Cancer and Metastasis Reviews

, Volume 16, Issue 1–2, pp 81–107

Molecular approaches to diagnosis and management of ovarian cancer

  • Roy M.T. Katso
  • Sanjiv Manek
  • Ken O'Byrne
  • Martin P. Playford
  • Valerie Le Meuth
  • Trivadi S. Ganesan
Article

Abstract

The recent advances in the understanding of the pathogenesis of ovarian cancer have been helpful in addressing issues in diagnosis, prognosis and management. The study of ovarian tumours by novel techniques such as immunohistochemistry, fluorescent in situ hybridisation, comparative genomic hybridisation, polymerase chain reaction and new tumour markers have aided the evaluation and application of new concepts into clinical practice. The correlation of novel surrogate tumour specific features with response to treatment and outcome in patients has defined prognostic factors which may allow the future design of tailored therapy based on a molecular profile of the tumour. These have also been used to design new approaches to therapy such as antibody targeting and gene therapy. The delineation of roles of c-erbB2, c-fms and other novel receptor kinases in the pathogenesis of ovarian cancer has led initially to the development of anti-c-erbB2 monoclonal antibody therapy. The discovery of BRCA1 and BRCA2 genes will have an impact in the diagnosis and the prevention of familial ovarian cancer. The important role played by recessive genes such as p53 in cancer has raised the possibility of restoration of gene function by gene therapy. Although the pathological diagnosis of ovarian cancer is still confirmed principally on morphological features, addition of newer investigations will increasingly be useful in addressing difficult diagnostic problems. The increasingly rapid pace of discovery of genes important in disease, makes it imperative that the evaluation of their contribution in the pathogenesis of ovarian cancer is undertaken swiftly, thus improving the overall management of patients and their outcome.

ovarian cancer molecular pathology 

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References

  1. 1.
    Fathalla MF: Incessant ovulation — a factor in ovarian neoplasia? Lancet 2: 163, 1971Google Scholar
  2. 2.
    Hutson R, Ramsdale J, Wells M: P53 protein expression in putative precursor lesions of epithelial ovarian-cancer. Histopathol 27: 367–371, 1995Google Scholar
  3. 3.
    Berchuck A, Boente MP, Kerns BJ, Kinney RB, Soper JT, Clarke PD, Bast RJ, Bacus SS: Ploidy analysis of epithelial ovarian cancers using image cytomerry. Gynecol Oncol 44: 61–65, 1992Google Scholar
  4. 4.
    Braly PS, Klevecz RR: Flow cytometric evaluation of ovarian-cancer. Cancer 71: 1621–1628, 1993Google Scholar
  5. 5.
    Gajewski WH, Fuller AF, Pastelley C, Flotte TJ, Bell DA: Prognostic-significance of DNA content in epithelial ovarian-cancer. Gynecol Oncol 53: 5–12, 1994Google Scholar
  6. 6.
    Erba E, Giordano M, Danova M, Mazzini G, Ubezio P, Torri V, Mangioni C, Landoni F, Bolis P, Tenti P, Franchi M, Babilonti L, Riccardi A, D'Incalci M: Cell kinetics of human ovarian cancer with in vivo administration of bromodeoxyuridine. Ann Oncol 5: 627–634, 1994Google Scholar
  7. 7.
    Rabbitts TH: Chromosomal translocations in human cancer. Nature 372: 143–149, 1994Google Scholar
  8. 8.
    Bast RJ, Boyer CM, Jacobs I, Xu FJ, Wu S, Wiener J, Kohler M, Berchunck A: Cell growth regulation in epithelial ovarian cancer. Cancer 71: 545–551, 1993Google Scholar
  9. 9.
    Pawson T, Schlessinger J: SH2 and SH3 domains. Curr Biol 3: 434–442, 1993Google Scholar
  10. 10.
    Pawson T: Protein modules and signalling networks. Nature 373: 573–579, 1995Google Scholar
  11. 11.
    Marshall CJ: Specificity of receptor tyrosine kinase signaling — transient versus sustained extracellular signal-regulated kinase activation. Cell 80: 179–185, 1995Google Scholar
  12. 12.
    Kohler M, Janz I, Wintzer HO, Wagner E, Bauknecht T: The expression of EGF receptors, EGF-like factors and c-myc in ovarian and cervical carcinomas and their potential clinical significance. Anticancer Res 9: 1537–1547, 1989Google Scholar
  13. 13.
    Bauknecht T, Kohler M, Janz M, Pfleiderer A: The occurrence of epidermal growth factor receptors and the characterization of EGF-like factors in human ovarian, endometrial, cervical and breast cancer. EGF receptors and factors in gynecological carcinomas. J Cancer Res Clin Oncol 115: 193–199, 1989Google Scholar
  14. 14.
    Scambia G, Benedetti PP, Battaglia F, Ferrandina G, Baiocchi G, Greggi S, De VR, Mancuso S: Significance of epidermal growth factor receptor in advanced ovarian cancer. J Clin Oncol 10: 529–535, 1992Google Scholar
  15. 15.
    Owens OJ, Stewart C, Leake RE, McNicol AM: A comparison of biochemical and immunohistochemical assessment of EGFR expression in ovarian cancer. Anticancer Res 12: 1455–1458, 1992Google Scholar
  16. 16.
    Berchuck A, Rodriguez GC, Kamel A, Dodge RK, Soper JT, Clarke PD, Bast RJ: Epidermal growth factor receptor expression in normal ovarian epithelium and ovarian cancer. I. Correlation of receptor expression with prognostic factors in patients with ovarian cancer. Am J Obstet Gynecol 164: 669–674, 1991Google Scholar
  17. 17.
    Van Dam P, Vergote IB, Lowe DG, Watson JV, van Damme P, van der Auwera J, Shepherd JH: Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor 1, and epidermal growth factor receptor in ovarian carcinoma. J Clin Pathol 47: 914–919, 1994Google Scholar
  18. 18.
    Devitt JL, Chew K, Sauter G, Waldman F, Benz CC: Prevalence and prognostic significance of HER2/neu and epidermal growth factor receptors in ovarian cancer. J Exp Clin Cancer Res 14: 329–334, 1995Google Scholar
  19. 19.
    Brady LW, Markoe AM, Woo DV, Rackover MA, Koprowski H, Steplewski Z, Peyster RG: Iodine 125 labeled anti-epidermal growth factor receptor-425 in the treatment of malignant astrocytomas. A pilot study, J Neurosurg Sci 34: 243–249, 1990Google Scholar
  20. 20.
    Brady LW, Miyamoto C, Woo DV, Rackover M, Emrich J, Bender H, Dadparvar S, Steplewski Z, Koprowski H, Black P, Lazzaro F, Nair S, McCormack T, Nieves J, Moarabito M, Eshloman J: Malignant astrocytomas treated with iodine-125 labeled monoclonal antibody 425 against epidermal growth factor receptor: a phase II trial. Int J Radiat Oncol Biol Phys 22: 225–230, 1992Google Scholar
  21. 21.
    Ekstrand AJ, Longo N, Hamid ML, Olson JJ, Liu L, Collins VP, James CD: Functional characterization of an EGF receptor with a truncated extracellular domain expressed in ghoblastomas with EGFR gene amplification. Oncogene 9: 2313–2320, 1994Google Scholar
  22. 22.
    Ekstrand AJ, Liu L, He J, Hamid ML, Longo N, Collins VP, James CD: Altered subcellular location of an activated and tumour-associated epidermal growth factor receptor. Oncogene 10: 1455–1460, 1995Google Scholar
  23. 23.
    Humphrey PA, Gangarosa LM, Wong AJ, Archer GE, Lund JM, Bjerkvig R, Laerum OD, Friedman HS, Bigner DD: Deletion-mutant epidermal growth factor receptor in human gliomas: effects of type II mutation on receptor function. Biochem Biophys Res Commun 178: 1413–1420, 1991Google Scholar
  24. 24.
    Moscatello DK, Holgadomadruga M, Godwin AK, Ramirez G, Gunn G, Zoltick PW, Biegel JA, Hayes RL, Wong AJ: Frequent expression of a mutant epidermal growth-factor receptor in multiple human tumors. Cancer Res 55: 5536–5539, 1995Google Scholar
  25. 25.
    Moscatello DK, Montgomery RB, Sundareshan P, McDanel H, Wong MY, Wong AJ: Transformation and altered signal-transduction by a naturally-occurring mutant EGF receptor. Oncogene 13: 85–96, 1996Google Scholar
  26. 26.
    Reist CJ, Archer GE, Kurpad SN, Wikstrand CJ, Vaidyanathan G, Willingham MC, Moscatello DK, Wong AJ, Bigner DD, Zalutsky MR: Tumor-specific anti-epidermal growth factor receptor variant III monoclonal antibodies: use of the tyramine-cellobiose radioiodination method enhances cellular retention and uptake in tumor xenografts. Cancer Res 55: 4375–4382, 1995Google Scholar
  27. 27.
    Lorimer IAJ, Wikstrand CJ, Batra SK, Bigner DD, Pastan I: Immunotoxins that torget on oncogenic mutant epidermal growth-factor receptor expressed in human tumors. Clin Cancer Res 1: 859–864, 1995Google Scholar
  28. 28.
    Akiyama T, Sudo C, Ogawara H, Toyoshima K, Yamamoto T: The product of the human c-erbB-2 gene: a 185-kilodalton glycoprotein with tyrosine kinase activity. Science 232: 1644–1646, 1986Google Scholar
  29. 29.
    Kraus MH, Popescu NC, Amsbaugh SC, King CR: Overexpression of the EGF receptor-related proto-oncogene erbB-2 in human mammary tumor cell lines by different molecular mechanisms. EMBO J 6: 605–610, 1987Google Scholar
  30. 30.
    Yamamoto T, Ikawa S, Akiyama T, Semba K, Nomura N, Miyajima N, Saito T, Toyoshima K: Similarity of protein encoded by the human c-erbB-2 gene to epidermal growth factor receptor. Nature 319: 230–234, 1986Google Scholar
  31. 31.
    Drebin JA, Link VC, Stern DF, Weinberg RA, Greene MI: Down-modulation of an oncogene protein product and reversion of the transformed phenotype by monoclonal antibodies. Cell 41: 697–706, 1985Google Scholar
  32. 32.
    Drebin JA, Link VC, Weinberg RA, Greene MI: Inhibition of tumor growth by a monoclonal antibody reactive with an oncogene-encoded tumor antigen. Proc Natl Acad Sci USA 83: 9129–9133, 1986Google Scholar
  33. 33.
    Wang DP, Konishi I, Koshiyama M, Nanbu Y, Iwai T, Nonogaki H, Mori T, Fujii S: Immunohistochemical localization of c-erbB-2 protein and epidermal growth factor receptor in normal surface epithelium, surface inclusion cysts, and common epithelial tumours of the ovary. Virchows Arch A Pathol Anat Histopathol 421: 393–400, 1992Google Scholar
  34. 34.
    Wang DP, Fujii S, Konishi I, Nanbu Y, Iwai T, Nonogaki H, Mori T: Expression of c-erbB-2 protein and epidermal growth factor receptor in normal tissues of the female genital tract and in the placenta. Virchows Arch A Pathol Anat Histopathol 420: 385–393, 1992Google Scholar
  35. 35.
    Slamon DJ, Godolphin W, Jones LA, Holt JA, Wong SG, Keith DE, Levin WJ, Stuart SG, Udove J, Ullrich A, Press MF: Studies of the HER-2/neu proto-oncogene in human breast and ovarian cancer. Science 244: 707–712, 1989Google Scholar
  36. 36.
    Meden H, Marx D, Rath W, Kuhn W, Hinney B, Schauer A: Overexpression of c-erbB-2 oncogene in primary ovarian cancers: incidence and prognostic significance in 243 patients. Geburtshilfe Frauenheilkd 52: 667–673, 1992Google Scholar
  37. 37.
    Meden H, Marx D, Rath W, Kron M, Fattahi MA, Hinney B, Kuhn W, Schauer A: Overexpression of the oncogene c-erbB-2 in primary ovarian cancer: evaluation of the prognostic value in a Cox proportional hazards multiple regression. Int J Gynecol Pathol 13: 45–53, 1994Google Scholar
  38. 38.
    Meden H, Marx D, Raab T, Kron M, Schauer A, Kuhn W: EGF-R and overexpression of the oncogene c-erbB-2 in ovarian cancer: immunohistochemical findings and prognostic value. J Obstet Gynaecol 21: 167–178, 1995Google Scholar
  39. 39.
    Haldane JS, Hird V, Hughes CM, Gullick WJ: c-erbB-2 oncogene expression in ovarian cancer. J Pathol 162: 231–237, 1990Google Scholar
  40. 40.
    Hruza C, Dobianer K, Beck A, Czerwenka K, Hanak H, Klcin M, Lcodolter S, Medl M, Mullauer ES, Prciscr J: HER-2 and INT-2 amplification estimated by quantitative PCR in paraffin-embedded ovarian cancer tissue samples. Eur J Cancer 29A: 1593–1597, 1993Google Scholar
  41. 41.
    Morali F, Cattabeni M, Tagliabue E, Campiglio M, Menard S, Marzola M, Lucchini V, Colombo N, Mangioni C, Redaelli L, Dincalci M: Overexpression of p185 is not related to erbB2 amplification in ovarian cancer. Ann Oncol 4: 775–779, 1993Google Scholar
  42. 42.
    Rubin SC, Finstad CL, Wong GY, Almadrones L, Planto M, Lloyd KO: Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis. Am J Obstet Gynecol 168: 162–169, 1993Google Scholar
  43. 43.
    Smith LH, Teng NN: Clinical applications of monoclonal antibodies in gynecologic oncology. Cancer 60: 2068–2074, 1987Google Scholar
  44. 44.
    Lichtenstein A, Berenson J, Gera JF, Waldburger K, Martinez MO, Berek JS: Resistance of human ovarian cancer cells to tumor necrosis factor and lymphokine-activated killer cells: correlation with expression of HER2/neu oncogenes. Cancer Res 50: 7364–7370, 1990Google Scholar
  45. 45.
    Yu D, Wolf JK, Scanlon M, Price JE, Hung MC: Enhanced c-erbB-2/neu expression in human ovarian cancer cells correlates with more severe malignancy that can be suppressed by E1A. Cancer Res 53: 891–898, 1993Google Scholar
  46. 46.
    Marth C, Muller HE, Greiter E, Cronauer MV, Zeimet AG, Doppler W, Eibl B, Hynes NE, Daxenbichler G: Gamma-interferon reduces expression of the protooncogene c-erbB-2 in human ovarian carcinoma cells. Cancer Res 50: 7037–7041, 1990Google Scholar
  47. 47.
    Hancock MC, Langton BC, Chan T, Toy P, Monahan JJ, Mischak RP, Shawver LK: A monoclonal antibody against the c-erbB-2 protein enhances the cytotoxicity of cis-diamminedichloroplatinum against human breast and ovarian tumor cell lines. Cancer Res 51: 4575–4580, 1991Google Scholar
  48. 48.
    Arteaga CL, Winnier AR, Poirier MC, Lopez LD, Shawver LK, Hurd SD, Stewart SJ: p185c-erbB-2 signal enhances cisplatin induced cytotoxicity in human breast carcinoma cells: association between an oncogenic receptor tyrosine kinase and drug-induced DNA repair. Cancer Res 54: 3758–3765, 1994Google Scholar
  49. 49.
    Shepard HM, Lewis GD, Sarup JC, Fendly BM, Maneval D, Mordenti J, Figari I, Kotts CE, Palladino MJ, Ullrich A, Slamon D: Monoclonal antibody therapy of human cancer: Taking the HER2 protooncogene to the clinic. J Clin Immunol 11: 117–127, 1991Google Scholar
  50. 50.
    Muss HB, Thor AD, Berry DA, Kute T, Liu ET, Koerner F, Cirrincione CT, Budman DR, Wood WC, Barcos M: c-erbB-2 expression and response to adjuvant therapy in women with node-positive early breast cancer. N Engl J Med 330: 1260–1266, 1994Google Scholar
  51. 51.
    McKenzie SJ, DeSombre KA, Bast BS, Hollis DR, Whitaker RS, Berchuck A, Boyer CM, Bast RJ: Serum levels of HER-2 neu (C-erbB-2) correlate with overexpression of p185neu in human ovarian cancer. Cancer 71: 3942–3946, 1993Google Scholar
  52. 52.
    Baselga J, Tripathy D, Mendelsohn J, Baughman S, Benz CC, Dantis L, Sklarin NT, Seidman AD, Hudis CA, Moore J, Rosen PP, Twaddell T, Henderson IC, Norton L: Phase-II study of weekly intravenous recombinant humanized anti-p185(her2) monoclonal-antibody in patients with her2/neu-overexpressing metastatic breast. J Clin Oncol 14: 737–744, 1996Google Scholar
  53. 53.
    Zhang YJ, Yu DH, Xia WY, Hung MC: Her-2/neu-targeting cancer-therapy via adenovirus-mediated cla delivery in an animal-model. Oncogene 10: 1947–1954, 1995Google Scholar
  54. 54.
    Prigent SA, Lemoine NR, Hughes CM, Plowman GD, Selden C, Gullick WJ: Expression of the c-erbB-3 protein in normal human adult and fetal tissues. Oncogene 7: 1273–1278, 1992Google Scholar
  55. 55.
    Simpson BJ, Phillips HA, Lessells AM, Langdon SP, Miller WR: c-erbB growth-factor-receptor proteins in ovarian tumours. Int J Cancer 64: 202–206, 1995Google Scholar
  56. 56.
    Simpsott BJ, Weatherill J, Miller EP, Lessells AM, Langdon SP, Miller WR: c-erbB-3 protein expression in ovarian tumours. Br J Cancer 71: 758–762, 1995Google Scholar
  57. 57.
    Tzahar E, Levkowitz G, Karunagaran D, Yi L, Peles E, Lavi S, Chang D, Liu N, Yayon A, Wen D, Yarden Y: ErbB-3 and ErbB-4 function as the respective low and high affinity receptors of all Neu differentiation factor/heregulin isoforms. J Biol Chem 269: 25226–25233, 1994Google Scholar
  58. 58.
    Peles E, Ben LR, Tzahar E, Liu N, Wen D, Yarden Y: Cell-type specific interaction of Neu differentiation factor (NDF/heregulin) with Neu/HER 2 suggests complex ligand-receptor relationships. Embo J 12: 961–971, 1993Google Scholar
  59. 59.
    Plowman GD, Whitney GS, Neubauer MG, Green JM, McDonadl VL, Todaro GJ, Shoyab M: Molecular cloning and expression of an additional epidermal growth factor receptor-related gene. Proc Natl Acad Sci USA 87: 4905–4909, 1990Google Scholar
  60. 60.
    Lemoine NR, Barnes DM, Hollywood DP, Hughes CM, Smith P, Dublin E, Prigent SA, Gullick WJ, Hurst HC: Expression of the ErbB3 gene product in breast cancer. Br J Cancer 66: 1116–1121, 1992Google Scholar
  61. 61.
    Chen XM, Levkowitz G, Tzahar E, Karunagaran D, Lavi S, Benbaruch N, Leitner O, Ratzkin BJ, Bacus SS, Yarden Y: An immunological approach reveals biological differences between the 2 ndf/heregulin receptors, erbB-3 and erbB-4. J Biol Chem 271: 7620–7629, 1996Google Scholar
  62. 62.
    Aboud PE, Lesur B, Rao KS, Baurain R, Trouet A, Schneider YJ: Cytotoxic activity of daunorubicin or vindesin conjugated to a monoclonal antibody on cultured MCF 7 breast carcinoma cells. Biochem Pharmacol 38: 641–648, 1989Google Scholar
  63. 63.
    Baselga J, Mendelsohn J: The epidermal growth factor receptor as a target for therapy in breast carcinoma. Breast Cancer Res Treat 29: 127–138, 1994Google Scholar
  64. 64.
    Benz CC, Scott GK, Sarup JC, Johnson RM, Tripathy D, Coronado E, Shepard HM, Osborne CK: Estrogen-dependent, tamoxifen-resistant tumorigenic growth of MCF-7 cells transfected with HER2/neu. Breast Cancer Res Treat 24: 85–95, 1993Google Scholar
  65. 65.
    Kacinski BM: CSF-1 and its receptor in ovarian, endometrial and breast-cancer. Ann Med 27: 79–85, 1995Google Scholar
  66. 66.
    Chambers SK, Kacinski BM: Messenger-RNA decay of macrophage-colony-stimulating factor in human ovarian carcinomas in vitro. J Soc Gynecol Invest 1: 310–316, 1994Google Scholar
  67. 67.
    Chambers SK, Wang YX, Gertz RE, Kacinski BM: Macrophage-colony-stimulating factor mediates invasion of ovarian-cancer cells though urokinase. Cancer Res 55: 1578–1585, 1995Google Scholar
  68. 68.
    Robinson D, He F, Pretlow T, Kung HJ: A tyrosine kinase profile of prostate carcinoma. Proc Natl Acad Sci USA 93: 5958–5962, 1996Google Scholar
  69. 69.
    Laval S, Butler R, Shelling AN, Hanby AM, Poulsom R, Ganesan TS: Isolation and characterisation of an epithelial specific receptor kinase from an ovarian cancer cell line. Cell Growth & Differentiation 5: 1173–1183, 1994Google Scholar
  70. 70.
    Wang XC, Katso R, Butler R, Hanby AM, Poulsom R, Jones T, Sheer D, Ganesan TS: H ryk, an unusual receptor kinase — isolation and analysis of expression in ovarian-cancer. Mol Med 2: 189–203, 1996Google Scholar
  71. 71.
    Johnson JD, Edman JC, Rutter WJ: A receptor tyrosine kinase found in breast carcinoma cells has an extracellular discoidin 1-like domain. Proc Natl Acad Sci 90: 5677–5681, 1993Google Scholar
  72. 72.
    Dimarco E, Cutuli N, Guerra L, Cancedda R, Deluca M: Molecular cloning of trkE, a novel trk-related putative tyrosine kinase receptor isolated from normal human keratinocytes and widely expressed by normal tissues. J Biol Chem 268: 24290–24295, 1993Google Scholar
  73. 73.
    Lai C, Lemke G: Structure and expression of the Tyro 10 receptor tyrosine kinase. Oncogene 9: 877–883, 1994Google Scholar
  74. 74.
    Karn T, Holtrich U, Brauninger U, Bohme B, Wolf G, Rubsamen-Waigmann H, Strebhardt K: Structure, expression and chromosomal mapping of TKT from man and mouse: A new subclass of receptor tyrosine kinases with a factor VIII like domain. Oncogene 8: 3443–3440, 1993Google Scholar
  75. 75.
    Poole S, Firtel RA, Lamar E, Rowekamp W: Sequence and expression of the discoidin I gene family in Dictyostelium discoideum. J Mol Biol 153: 273–289, 1981Google Scholar
  76. 76.
    Rosen SD, Kafka JA, Simpson DL, Barondes WH: Developmentally regulated carbohydrate binding protein in Dictyostelium discoideum. Proc Natl Acad Sci USA 70: 2554–2557, 1973Google Scholar
  77. 77.
    Springer WR, Cooper DNW, Barondes SH: Discoidin I is implicated in cell-substratum attachment and ordered cell migration of dictyostclium discoideum and resembles fibronectin. Cell 39: 557–564, 1984Google Scholar
  78. 78.
    Alexander S, Sydow LM, Wessels D, Soll DR: Discoidin proteins of Dictyostelium are necessary for normal cytoskeletal organization and cellular morphology during aggregation. Differentiation 51: 149–161, 1992Google Scholar
  79. 79.
    Arai M, Scandella D, Hoyer LW: Molecular basis of Factor VIII inhibition by human antibodies. Antibodies that bind to factor VIII light chain prevent the interaction of factor VIII with phospholipids. J Clin Invest 83: 1978–1984, 1989Google Scholar
  80. 80.
    Stubbs JD, Lekutis C, Singer KL, Anhthu B, Yuzuki D, Srinivasan U, Parry G: cDNA cloning of a mouse mammary epithelial cell surface protein reveals the existence of epidermal growth factor-like domains linked to factor VIII-like sequences. Proc Natl Acad Sci 87: 8417–8421, 1990Google Scholar
  81. 81.
    Playford MP, Butler RJ, Wang XC, Katso RM, Cooke IE, Ganesan TS: The genomic structure of discoidin receptor tyrosine kinase. Genome Res 6: 620–627, 1996Google Scholar
  82. 82.
    Alves F, Vogel W, Mossic K, Millauer B, Hofler H, Ullrich A: Distinct structural characteristics of discoidin I subfamily receptor tyrosine kinases and complementary expression in human cancer. Oncogene 10: 609–618, 1995Google Scholar
  83. 83.
    Barker KT, Martindale JE, Mitchell PJ, Kamaalti T, Page MJ, Phippard DJ, Dale TC, Gustrrson BA, Crompton MR: Expression patterns of the novel receptor-like tyrosine kinase, DDR, in human breast tumours. Oncogene 10: 569–575, 1995Google Scholar
  84. 84.
    Chou Y-H, Hayman MJ: Characterisation of a member of the immunoglobulin gene superfamily that possibly represents an additional class of growth factor receptor. Proc Natl Acad Sci USA 88: 4897–4901, 1991Google Scholar
  85. 85.
    Gibbs JB, Sigal IS, Poc M, Scolnick EM: Intrinsic GTPase activity distinguishes normal and oncogenic ras p21 molecules. Proc Natl Acad Sci USA 81: 5704–5708, 1984Google Scholar
  86. 86.
    Thor A, Ohuchi N, Hand PH, Callahan R, Weeks MO, Theillet C, Lidereau R, Escot C, Page DL, Vilasi V, Schlom J: Ras gene alterations and enhanced levels of ras p21 expression in a spectrum of benign and malignant human mammary tissues. Lab Invest 55: 603–615, 1986Google Scholar
  87. 87.
    Heighway J, Thatcher N, Cerny T, Hasleton PS: Genetic predisposition to human lung cancer. Br J Cancer 53: 453–457, 1986Google Scholar
  88. 88.
    Krontiris TG, DiMartino NA, Colb M, Mitcheson HD, Parkinson DR: Human restriction fragment length polymorphisms and cancer risk assessment. J Cell Biochem 30: 319–329, 1986Google Scholar
  89. 89.
    Krontiris TG, DiMartino NA, Mitcheson HD, Lonergan JA, Begg C, Parkinson DR: Human hypervariable sequences in risk assessment: rare Ha-ras alleles in cancer patients. Environ Health Perspect 76: 147–153, 1987Google Scholar
  90. 90.
    Lidereau R, Escot C, Theillet C, Champeme MH, Brunet M, Gest J, Callahan R: High frequency of rare alleles of the human c-Ha-ras-1 proto-oncogene in breast cancer patients. J Natl Cancer Inst 77: 697–701, 1986Google Scholar
  91. 91.
    Theillet C, Lidereau R, Escot C, Hutzell P, Brunel M, Gest J, Schlom J, Callahan R: Loss of a c-H-ras-1 allele and aggressive human primary breast carcinomas. Cancer Res 46: 4776–4781, 1986Google Scholar
  92. 92.
    O'Briant K, Chrysson N, Hunter V, Tyson F, Tanner M, Daly L, George SL, Berchuck A, Soper J, Fowler W: Ha-ras polymorphisms in epithelial ovarian cancer. Gynecol Oncol 45: 299–302, 1992Google Scholar
  93. 93.
    Phelan CM, Rebbeck TR, Weber BL, Devilee P, Ruttledge MH, Lynch HT, Lenoir GM, Stratton MR, Easton DF, Ponder BAJ, Cannonalbright L, Larsson C, Goldgar DE, Narod SA: Ovarian-cancer risk in brea1 carriers is modified by the hras1 variable number of tandem repeat (vntr) locus. Nat Genet 12: 309–311, 1996Google Scholar
  94. 94.
    Foulkes WD, Englefield P, Campbell IG: Mutation analysis of RASK and the ‘FLR exon’ of NF1 in sporadic ovarian carcinoma. Eur J Cancer 30A: 528–530, 1994Google Scholar
  95. 95.
    Mok SCH, Bell DA, Knapp RC, Fishbaugh PM, Welch WR, Muto MG, Berkowitz RS, Tsao SW: Mutation of k-ras protooncogene in human ovarian epithelial tumors of borderline malignancy. Cancer Res 53: 1489–1492, 1993Google Scholar
  96. 96.
    Teneriello MG, Ebina M, Linnoila RI, Henry M, Nash JD, Park RC, Birrer MJ: p53 and Ki-ras gene mutations in epithelial ovarian neoplasms. Cancer Res 53: 3103–3108, 1993Google Scholar
  97. 97.
    Cuatrecasas M, Matias GX, Prat J: Synchronous mucinous tumors of the appendix and the ovary associated with pseudomyxoma peritonei. A clinicopathologic study of six cases with comparative analysis of c-Ki-ras mutations. Am J Surg Pathol 20: 739–746, 1996Google Scholar
  98. 98.
    Yaginuma Y, Yamashita K: Immunohistochemical studies of ras oncogene product p21 in human ovarian tumors. Nippon Sanka Fujinka Gakkai Zasshi 41: 1409–1416, 1989Google Scholar
  99. 99.
    Yaginuma Y, Yamashita K, Kuzumaki N, Fujita M, Shimizu T: Ras oncogene product p21 expression and prognosis of human ovarian tumors. Gynecol Oncol 46: 45–50, 1992Google Scholar
  100. 100.
    Kotylo PK, Michael H, Fineberg N, Sutton G, Roth LM: Flow cytometric analysis of DNA content and RAS PZI oncoprotein expression in ovarian neoplasms. Int J Gynecol Pathol 11: 30–37, 1992Google Scholar
  101. 101.
    Scambia G, Catozzi L, Panici PB, Ferrandina G, Coronetta F, Barozzi R, Baiocchi G, Uccelli L, Piffanelli A, Mancuso S: Expression of ras oncogene p21 protein in normal and neoplastic ovarian tissues: correlation with histopathologic features and receptors for estrogen, progesterone, and epidermal growth factor. Am J Obstet Gynecol 168: 71–78, 1993Google Scholar
  102. 102.
    Watson JV, Curling OM, Munn CF, Hudson CN: Oncogene expression in ovarian cancer: a pilot study of c-myc oncoprotein in serous papillary ovarian cancer. Gynecol Oncol 28: 137–150, 1987Google Scholar
  103. 103.
    Sasano H, Nagura H, Silverberg SG: Immunolocalization of c-myc oncoprotein in mucinous and serous adenocarcinomas of the ovary. Hum Pathol 23: 491–495, 1992Google Scholar
  104. 104.
    Baker VV, Borst MP, Dixon D, Hatch KD, Shingleton HM, Miller D: c-myc amplification in ovarian cancer. Gynecol Oncol 38: 340–342, 1990Google Scholar
  105. 105.
    Sasano H, Garrett CT, Wilkinson DS, Silverberg S, Comerford J, Hyde J: Protooncogene amplification and tumor ploidy in human ovarian neoplasms. Hum Pathol 21: 382–391, 1990Google Scholar
  106. 106.
    Schreiber G, Dubeau L: C-mye proto-oncogene amplification detected by polymerase chain reaction in archival human ovarian carcinomas. Am J Pathol 137: 653–658, 1990Google Scholar
  107. 107.
    Shelling AN, Cooke IF., Ganesan TS: The genetic-analysis of ovarian cancer. Br J Cancer 72: 521–527, 1995Google Scholar
  108. 108.
    Ford D, Easton DF: The genetics of breast and ovarian-cancer. Br J Cancer 72: 805–812, 1995Google Scholar
  109. 109.
    Miki Y, Swensen J, Shattuckeidens D, Futreal PA, Harshman K, Tavtigian S, Liu OY, Cochran C, Bennett LM, Ding W, Bell R, Rosenthal J, Hussey C, Tran T, McClure M, Frye C, Hattier T, Phelps R, Haugenstrano A, Katcher H, Yakumo K, Gholami Z, Shaffer D, Stone S, Bayer S, Wray C, Bogden R, Dayananth P, Ward J, Tonin P, Narod S, Bristow PK, Norris FH, Helverin: A strong candidate for the breast and ovarian-cancer susceptibility gene brcal. Science 266: 66–71, 1994Google Scholar
  110. 110.
    Tavtigian SV, Simard J, Rommens J, Couch F, Shattuckeidens D, Neuhausen S, Merajver S, Thorlacius S, Offil K, Stoppalyonnet D, Belanger C, Bell R, Berry S, Bogden R, Chen Q, Davis T, Dumont M, Frye C, Hattier T, Jammulapati S, Janceki T, Jiang P, Kehrer R, Leblanc JF, Mitchell JT, McArthurmorrison J, Nguyen K, Peng Y, Samson C, Schroeder: The complete brca2 gene and mutations in chromosome 13q-linked kindreds. Nature Genet 12: 333–337, 1996Google Scholar
  111. 111.
    Steeg P: Granin expectations in breast-cancer. Nature Genet 12: 223–225, 1996Google Scholar
  112. 112.
    Bradley A, Sharan SK: Breal protein products — secreted tumor suppressors. Nature Genet 13: 268–269, 1996Google Scholar
  113. 113.
    Chapman MS, Verma IM: Transcriptional activation by brcal. Nature 382: 678–679, 1996Google Scholar
  114. 114.
    Hakem R, Delapompa JL, Sirard C, Mo R, Woo M, Hakem A, Wakeham A, Potter J, Reitmair A, Billia F, Firpo E, Hui CC, Roberts J, Rossant J, Mak TW: The tumor-suppressor gene brcal is required for embryonic cellular proliferation in the mouse. Cell 85: 1009–1023, 1996Google Scholar
  115. 115.
    Jensen RA, Thompson ME, Jetton TL, Szabo CI, Vandermeer R, Helou B, Tronick SR, Page DL, King MC, Holt JT: Brcal is secreted and exhibits propertics of a granin. Nature Genet 12: 303–308, 1996Google Scholar
  116. 116.
    Rao VN, Shao NS, Ahmad M, Reddy ESP: Antisense RNA to the putative tumor-suppressor gene brcal transforms mouse fibroblasts. Oncogene 12: 523–528, 1996Google Scholar
  117. 117.
    Shao NS, Chai YL, Shyam E, Reddy P, Rao NV: Induction of apoptosis by the tumor-suppressor protein brcal. Oncogene 13: 1–7, 1996Google Scholar
  118. 118.
    Scully R, Ganesan S, Brown M, Decaprio JA, Cannistra SA, Feunteun J, Schnitt S, Livingston DM: Location of brcal in human breast and ovarian cancer cells. Science 272: 123–125, 1996Google Scholar
  119. 119.
    Xu CF, Solomon E: Mutations of the brcal gene in human cancer. Semin Cancer Biol 7: 33–40, 1996Google Scholar
  120. 120.
    Fitzgerald MG, MacDonald DJ, Krainer M, Hoover I, Oneil E, Unsal H, Silvaarrieto S, Finkelstein DM, Beerromero P, Englert C, Sgroi DC, Smith BL, Younger JW, Garber JE, Duda RB, Mayzel KA, Isselbacher KJ, Friend SH, Haber DA: Germ-line brcal mutations in jewish and non-jewish women with early-onset breast-cancer. N Engl J Med 334: 143–149, 1996Google Scholar
  121. 121.
    Struewing JP, Tarone RE, Brody LC, Li FP, Boice JD: Brcal mutations in young-women with breast-cancer. Lancet 347: 1493–1493, 1996Google Scholar
  122. 122.
    Offit K, Gilewski T, McGuire P, Schluger A, Hampel H, Brown K, Swensen J, Neuhausen S, Skolnick M, Norton L, Goldgar D: Germline brcal 185delag mutations in jewish women with breast-cancer. Lancet 347: 1643–1645, 1996Google Scholar
  123. 123.
    Lancaster JM, Cochran CJ, Brownlee HA, Evans AC, Berchuck A, Futreal PA, Wiseman RW: Detection of brcal mutations in women with early onset ovarian-cancer by use of the protein truncation test. J Natl Cancer Inst 88: 552–554, 1996Google Scholar
  124. 124.
    Shattuckeidens D, McClure M, Simard J, Labrie F, Narod S, Couch F, Hoskins K, Weber B, Castilla L, Erdos M, Brody L, Friedman L, Ostermeyer E, Szabo C, King MC, Jhanwar S, Offit K, Norton L, Gilewski T, Lubin M, Oshorne M, Black D, Boyd M, Steel M, Ingles S, Haile R, Lindblom A, Olsson H, Borg A, Bishop DT, Solomon E, Radiee P, Spatti G: A collaborative survey of 80 mutations in the brcal breast-cancer and ovarian-cancer susceptibility gene — implications for presymptomatic testing and screening. JAMA 273: 535–541, 1995Google Scholar
  125. 125.
    Steiehengersdorf E, Gallion HH, Ford D, Girodet C, Easton DF, Dicioeeio RA, Evans G, Ponder MA, Pye C, Mazoyer S, Noguchi T, Karengueven F, Sobol H, Hardouin A, Bignon YJ, Piver MS, Smith SA, Ponder BAJ: Familial sitespecific ovarian-cancer is linked to brcal on 17q12–21. Am J Hum Genet 55: 870–875, 1994Google Scholar
  126. 126.
    Merajver SD, Pham TM, Caduff RF, Chen M, Poy EL, Cooney KA, Weber BL, Collins FS, Johnston C, Frank TS: Somatic mutations in the BRCA1 gene in sporadic ovarian tumours. Nat Genet 9: 439–443, 1995Google Scholar
  127. 127.
    Takahashi H, Behbakht K, McGovern PE, Chiu HC, Couch FJ, Weber BL, Friedman LS, King MC, Furusato M, LiVolsi VA, Menzin AW, Liu P, Benjamin I, Morgan MA, King SA, Rebane BA, Cardonick A, Mikuta JJ, Rubin SC, Boyd J: Mutation analysis of the BRCA1 gene in ovarian cancers. Cancer Res 55: 2998–3002, 1995Google Scholar
  128. 128.
    Wooster R, Bignell G, Lancaster J, Swift S, Seal S, Mangion J, Collins N, Gregory A, Gumbs C, Michlem G, Barfoot R, Hamoudi R, Patel S, Rice C, Biggs P, Hashim Y, Smith A, Conner F, Arason A, Gudmundsson J, Ficenec D, Kelsell D, Ford D, Tonin P, Bishop DT, Spurr NK, Ponder BAJ, Eeles R, Peto J, Devilee P, Cornelisse C, Lynch H, Narod S, Lenoir G, Egilsson V: Identification of the breast-cancer susceptibility gene brca2. Nature 379: 749–749, 1996Google Scholar
  129. 129.
    Berman DB, Costalas J, Schultz DC, Grana G, Daly M, Godwin AK: A common mutation in brca2 that predisposes to a variety of cancers is found in both jewish ashkenazi and non-jewish individuals. Cancer Res 56: 3409–3414, 1996Google Scholar
  130. 130.
    Neuhausen S, Gilewski T, Norton L, Tran T, McGuire P, Swensen J, Hampel H, Borgen P, Brown K, Skolnick M, Shattuckeidens D, Jhanwar S, Goldgar D, Offit K: Recurrenl brca2 6174dell mutations in ahskenazi jewish women affected by breast-cancer. Nature Genet 13: 126–128, 1996Google Scholar
  131. 131.
    Lancaster JM, Wooster R, Mangion J, Phelan CM, Cochran C, Gumbs C, Seal S, Barfoot R, Collins N, Bignell G, Patel S, Hamoudi R, Larsson C, Wiseman RW, Berchuck A, Iglehart JD, Marks JR, Ashworth A, Stratton MR, Futreal PA: Brca2 mutations in primary breast and ovarian cancers. Nature Genet 13: 238–240, 1996Google Scholar
  132. 132.
    Takahashi H, Chin HC, Bandera CA, Behbakht K, Liu PC, Couch FJ, Weber BL, Livolsi VA, Furusato M, Rebane BA, Cardonick A, Benjamin I, Morgan MA, King SA, Mikuta JJ, Rubin SC, Boyd J: Mutations of the brca2 gene in ovarian carcinomas. Cancer Res 56: 2738–2741, 1996Google Scholar
  133. 133.
    Foster KA, Harrington P, Kerr J, Russell P, Dicioccio RA, Scott IV, Jacobs I, Chenevixtrench G, Ponder BAJ, Gayther SA: Somatic and germline mutations of the brca2 gene in sporadic ovarian-cancer. Cancer Res 56: 3622–3625, 1996Google Scholar
  134. 134.
    Pejovic T: Genetic changes in ovarian cancer. Ann Med 27: 73–78, 1995Google Scholar
  135. 135.
    Cliby W, Ritland S, Hartmann L, Dodson M, Halling KC, Keeney G, Podratz KC, Jenkins RB: Human epithelial ovarian cancer allelotype. Cancer Res 53: 2393–2398, 1993Google Scholar
  136. 136.
    Harris CC, Hollstein M: Clinical implications of the p53 tumor-suppressor gene. N Engl J Med 329: 1318–1327, 1993Google Scholar
  137. 137.
    Donehower LA, Bradley A: The tumor-suppressor p53. Biochim Biophys Acta 1155: 181–205, 1993Google Scholar
  138. 138.
    Greenblatt MS, Bennett WP, Hollstein M, Harris CC: Mutations in the p53 tumor-suppressor gene — clues to cancer etiology and molecular pathogenesis. Cancer Res 54: 4855–4878, 1994Google Scholar
  139. 139.
    Harris CC: P53 tumor-suppressor gene — from the basic research laboratory to the clinic — an abridged historical-perspective. Carcinogenesis 17: 1187–1198, 1996Google Scholar
  140. 140.
    Lane DP: Cancer. p53, guardian of the genome. Nature 358, 15–16, 1992Google Scholar
  141. 141.
    Kastan MB, Canman CE, Leonard CJ: P53, cell-cycle control and apoptosis — implications for cancer. Cancer Metastasis Rev 14: 3–15, 1995Google Scholar
  142. 142.
    Skilling JS, Sood A, Niemann T, Lager DJ, Buller RE: An abundance of p53 null mutations in ovarian-carcinoma. Oncogene 13: 117–123, 1996Google Scholar
  143. 143.
    Lane MA, Abdellatif N, Baunoch DA, Kaufman LM, Adelson MD, Reece MT: Deletion of tp53 exon-1 in human epithelial ovarian-cancer. Oncol Rep 2: 529–536, 1995Google Scholar
  144. 144.
    Buller RE, Anderson B, Connor JP, Robinson R: Familial ovarian cancer. Gynecol Oncol 51: 160–166, 1993Google Scholar
  145. 145.
    Buller RE, Skilling JS, Kaliszewski S, Niemann T, Anderson B: Absence of significant germ-line p53 mutations in ovarian-cancer patients. Gynecol Oncol 58: 368–374, 1995Google Scholar
  146. 146.
    Jolly KW, Malkin D, Douglas EC, BrowSinclair AE, Look AT: Splice-site mutation of the p53 gene in a family with hereditary breast-ovarian cancer. Oncogene 9: 97–102, 1994Google Scholar
  147. 147.
    Kupryjanczyk J, Bell DA, Yandell DW, Scully RE, Thor AD: p53 expression in ovarian borderline tumors and stage I carcinomas. Am J Clin Pathol 102: 671–676, 1994Google Scholar
  148. 148.
    Kupryjanczyk J, Bell DA, Dimeo D, Beauchamp R, Thor AD, Yandell DW: p53 gene analysis of ovarian borderline tumors and stage I carcinomas. Hum Pathol 26: 387–392, 1995Google Scholar
  149. 149.
    Berchuck A, Kohler MF, Hopkins MP, Humphrey PA, Robboy SJ, Rodriguez GC, Soper JT, Clarkepearson DL, Bast RC: Overexpression of p53 is not a feature of benign and early-stage borderline epithelial ovarian-tumors. Gynecol Oncol 52: 232–236, 1994Google Scholar
  150. 150.
    Lee JH, Kang YS, Park SY, Kim BG, Lee ED, Lee KH, Park KB, Kavanagh JJ, Wharton JT: P53 mutation in epithelial ovarian-carcinoma and borderline ovarian tumor. Cancer Genet Cytogenet 85: 43–50, 1995Google Scholar
  151. 151.
    Wertheim I, Muto MG, Welch WR, Bell DA, Berkowitz RS, Mok SC: P53 gene mutation in human borderline epithelial ovarian-tumors. J Natl Cancer Inst 86: 1549–1551, 1994Google Scholar
  152. 152.
    Zheng J, Benediet WF, Xu HJ, Hu SX, Kim TM, Velicescu M, Wan M, Cofer KF, Dubeau L: Genetic disparity between morphologically benign cysts contiguous to ovarian carcinomas and solitary cystadenomas [see comments]. J Natl Cancer Inst 87: 1146–1153, 1995Google Scholar
  153. 153.
    Marcelli AR, Demopoulos RI, Goswami S, Mittal KR: Comparison of p53 and mibl expression in benign and borderline areas of ovarian serous tumors. Int J Gynecol Pathol 15: 39–44, 1996Google Scholar
  154. 154.
    Liu E, Nuzum C: Molecular sleuthing: tracking ovarian cancer progression. J Natl Cancer Inst 87: 1099–1101, 1995Google Scholar
  155. 155.
    Jacobs IJ, Kohler MF, Wiscman RW, Marks JR, Whitaker R, Kerns BA, Humphrey P, Berchuck A, Ponder BA, Bast RJ: Clonal origin of epithelial ovarian carcinoma: analysis by loss of heterozygosity. p53 mutation, and X-chromosome inactivation. J Natl Cancer Inst 84: 1793–1798, 1992Google Scholar
  156. 156.
    Kupryjanczyk J, Thor AD, Beauchamp R, Poremba C, Seully RE, Yandell DW: Ovarian, petitoneal, and endometrial serous carcinoma — clonal origin of multiforcal discase. Mod Pathol 9: 166–173, 1996Google Scholar
  157. 157.
    Mok CH, Tsao SW, Knapp RC, Fishbaugh PM, Lau CC: Unifocal origin of advanced human epithelial ovarian cancers. Cancer Res 52: 5119–5122, 1992Google Scholar
  158. 158.
    Fujita M, Enomoto T, Wada H, Inoue M, Okudaira Y, Shroyer KR: Application of clonal analysis — differential-diagnosis for synchronous primary ovarian and endometrial cancers and metastatic cancer. Am J Clin Pathol 105: 350–359, 1996Google Scholar
  159. 159.
    Kohler MF, Kerns B-JM, Humphrey PA, marks JR, Bast RC, Berchuck A: Mutation and overexpression of p53 in carly-stage epithelial ovarian cancer. Obstet Gynecol 81: 643–650, 1993Google Scholar
  160. 160.
    Kupryjanczyk J, Thor AD, Beauchamp R, Merritt V, Edgerton SM, Bell DA, Yandell DW: p53 gene mutations and protem accumulation in human ovarian cancer. Proc Natl Acad Sci USA 90: 4961–4965, 1993Google Scholar
  161. 161.
    Bosari S, Viale G, Radaelli U, Bossi P, Bonoldi E, Coggi G: p53 accumulation in ovarian carcinomas and its prognostic implications. Hum Pathol 24: 1175–1179, 1993Google Scholar
  162. 162.
    Hartmann LC, Podratz KC, Kecney GL, Kamel XA, Edmonson JH, Grill JP, Su JQ, Katzmann JA, Roche PC: Prognostic significance of p53 immunostaining in epithelial ovarian cancer. J Clin Oncol 12: 64–69, 1994Google Scholar
  163. 163.
    Henriksen R, Strang P, Wilander E, Backstrom T, Tribukait B, Oberg K: P53 expression in epithelial ovarian neoplasms — relationship to clinical and pathological parameters, ki-67 expression and flow-eytometry. Gynecol Oncol 53: 301–306, 1994Google Scholar
  164. 164.
    Niwa K, Itoh M, Murase T, Morishita S, Itoh N, Mori H, Tamaya T: Alteration of p53 gene in ovarian-carcinoma — clinicopathological correlation and prognostic-significance. Br J Cancer 70: 1191–1197, 1994Google Scholar
  165. 165.
    Sheridan E, Sileocks P, Smith J, Hancock BW, Goyns MH: P53 mutation in a series of epithelial ovarian cancers from the UK, and its prognostic-significance. Eur J Cancer 30A: 1701–1704, 1994Google Scholar
  166. 166.
    Renninson J, Baker BW, McGown AT, Murphy D, Norton JD, Fox BW, Crowther D: Immunohistochemical detection of mutant p53 protein in peithelial ovarian cancer using polyclonal antibody CMI: correlation with histopathology and clinical features. Br J Cancer 69: 609–612, 1994Google Scholar
  167. 167.
    Reles A, Press MF, Schonborn I, Lichrenegger W, Strohmeyer T: Accumulation of p53 in ovarian-cancer — correlation with histopathological and clinical-data. Gynckol Geburtshilfliche Rundsch 35: 93–97, 1995Google Scholar
  168. 168.
    Levesque MA, Katsaros D, Yu H, Zola P, Sismondi P, Giardina G, Diamandis EP: Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian-carcinoma. Cancer 75: 1327–1338, 1995Google Scholar
  169. 169.
    Levesque MA, Diamandis EP, Yu H, Zola P, Sismondi P, Giardina G, Katsaros D: Immunofluorometrically quantified p53 protein as a prognostic indicator in ovarian-carcinoma. Clin Chem 41: 224, 1995Google Scholar
  170. 170.
    Reles A, Schmider A, Press MF, Schonborn I, Friedmann W, Huberschumacher S, Strohmeyer T, Lichtenegger W: Immunostaining of p53 protein in ovarian-carcinoma — correlation with histopathological data and clinical outcome. J Cancer Res Clin Oncol 122: 489–494, 1996Google Scholar
  171. 171.
    Herod JJO, Eliopoulos AG, Warwick J, Nicdobitek G, Young LS, Kerr DJ: The prognostic-significance of bcl-2 and p53 expression in ovarian-carcinoma. Cancer Res 56: 2178–2184, 1996Google Scholar
  172. 172.
    Diehold J, Baretton G, Felehner M, Maier W, Dopfer K, Schmidt M, Lohrs U: Bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas. Am J Clin Pathol 105: 341–349, 1996Google Scholar
  173. 173.
    Berchuck A, Bast RC: P53-based gene-therapy of ovarian-cancer — magic bullet. Gynecol Oncol 59: 169–170, 1995Google Scholar
  174. 174.
    Mujoo K, Maneval DC, Anderson SC, Gutterman JU: Adenoviral-mediated p53 tumor-suppressor gene-therapy of human ovarian carcinoma. Oncogene 12: 1617–1623, 1996Google Scholar
  175. 175.
    Santoso JT, Tang DC, Lane SB, Hung J, Reed DJ, Muller CY, Carbone DP, Lucci JA, Miller DS, Mathis JM: Adenovirus-based p53 gene-therapy in ovarian-cancer. Gynecol Oncol 59: 171–178, 1995Google Scholar
  176. 176.
    Costa I, Matiasguiu X, Musulen E, Cuatrecasas M, Prat J: P53 expression in ovarian epithelial stromal tumors. Lab Invest 72: 88, 1995Google Scholar
  177. 177.
    Liu FS, Ho ESC, Lai CR, Chen JT, Shih RTP, Yang CH, Tsao CM: Overexpression of p53 is not a feature of ovarian granulosa-cell tumors. Gynecol Oncol 61: 50–53, 1996Google Scholar
  178. 178.
    Marx L, Dietl J, Horny HP: Overexpression or mutation of the p53 tumor-suppressor gene does not occur in malignant ovarian germ-cell tumors. Cancer 78: 179–180, 1996Google Scholar
  179. 179.
    Lutzker S, Levine A: A functionally inactive p53 protein in teratocarcinoma cells is activated by either DNA-damage or cellular-differentiation. Nat Med 2: 804–810, 1996Google Scholar
  180. 180.
    Tavassoli M, Ruhrberg C, Beaumont V, Reynolds K, Kirkham N, Collins WP, Farzanch F: Whole chromosome 17 loss in ovarian cancer. Genes Chromosom Cancer 8: 195–198, 1993Google Scholar
  181. 181.
    Phillips N, Ziegler M, Saha B, Xynos F: Allelic loss on chromosome 17 in human ovarian cancer. Int J Cancer 54: 85–91, 1993Google Scholar
  182. 182.
    Jacobs IJ, Smith SA, Wiseman RW, Futreal PA, Harrington T, Osborne RJ, Leech V, Molyneux A, Berchuck A, Ponder BA, Bast RC: A delction unit on chromosome 17q in epithelial ovarian tumors distal to the familial breast/ovarian cancer locus. Cancer Res 53: 1218–1221, 1993Google Scholar
  183. 183.
    Tangir J, Muto M, Berkowitz R, Welch W, Bell D, Mok S: A 400 kb novel deletion unit centrimetric to the brcal gene in sporadic epithelial ovarian-cancer. Oncogene 12: 735–740, 1996Google Scholar
  184. 184.
    Pieretti M, Powell DE, Galhon HH, Conway PS, Case EA, Turker MS: Hypermethylation at a chromosome 17 ‘hot spot’ is a common event in ovarian cancer. Hum Pathol 26: 398–401, 1995Google Scholar
  185. 185.
    Schultz DC, Vanderveer L, Berman DB, Hamilton TC, Wong AJ, Godwin AK: Identification of 2 candidate tumor-suppressor genes on chromosome 17p13.3. Cancer Res 56: 1997–2002, 1996Google Scholar
  186. 186.
    Phillips NJ, Ziegler MR, Radford DM, Fair KL, Steinbrueek T, Xynos FP, Doniskeller H: Allelic deletion on chromosome 17p13.3 in early ovarian-cancer. Cancer Res 56: 606–611, 1996Google Scholar
  187. 187.
    Dodson MK, Cliby WA, Xu HJ, DeLacey KA, Hu SX, Keeney GL, Li J, Podratz KC, Jenkins RB, Benedict WF: Evidence of functional RB protein in epithelial ovarian carcinomas despite loss of heterozygosity at the RB locus. Cancer Res 54: 610–613, 1994Google Scholar
  188. 188.
    Kim TM, Benedict WF, Xu HJ, Hu SX, Gosewehr J, Velicescu M, Yin E, Zheng J, D'Ablaing G, Dubeau L: Loss of heterozygosity on chromosome 13 is common only in the biologically most aggressive subtypes of ovarian epithelial tumors and is associated with normal retinoblastoma gene expression. Cancer Res 54: 605–609, 1994Google Scholar
  189. 189.
    Li SB, Schwartz PE, Lee WH, Yang FT: Allele loss at the retinoblastoma locus in human ovarian cancer. J Natl Cancer Inst 83: 637–640, 1991Google Scholar
  190. 190.
    Liu Y, Heyman M, Wang Y, Falkmer U, Hising C, Szekely L, Einhorn S: Molecular analysis of the retinoblastoma gene in primary ovarian cancer cells. Int J Cancer 58: 663–667, 1994Google Scholar
  191. 191.
    Yang FT, Li S, Han H, Schwartz PE: Frequent loss of heterozygosity on chromosomes Xp and 13q in human ovarian cancer. Int J Cancer 52: 575–580, 1992Google Scholar
  192. 192.
    Yangfeng TL, Li SB, Han H, Schwartz P: Frequent loss of heterozygosity on chromosome-Xp and chromosome-13q in human ovarian-cancer. Int J Cancer 52: 575–580, 1992Google Scholar
  193. 193.
    Chenevix-Trench G, Leary J, Kerr J, Michel J, Kefford R, Hurst T, Parsons PG, Friedlander M, Khoo SK: Frequent loss of heterozygosity on chromosome 18 in ovarian adenocarcinoma which does not always include the DCC locus. Oncogene 7: 1059–1065, 1992Google Scholar
  194. 194.
    Enomoto T, Fujita M, Cheng C, Nakashima R, Ozaki M, Inoue M, Nomura T: Loss of expression and loss of heterozygosity in the DCC gene in neoplasms of the human female reproductive-tract. Br J Cancer 71: 462–467, 1995Google Scholar
  195. 195.
    Yamashita T, Yaginuma Y, Yamashita K, Fujita M, Ishikawa M: DCC gene alterations in histological types and clinical stages of epithelial ovarian-cancer. Int J Oncol 9: 291–296, 1996Google Scholar
  196. 196.
    Hunter T, Pines J: Cyclins and cancer. II: Cyclin D and CDK inhibitors come of age. Cell 79: 573–582, 1994Google Scholar
  197. 197.
    Devlin J, Elder PA, Gabra H, Steel CM, Knowles MA: High-frequency of chromosome-9 deletion in ovarian-cancer — evidence for 3 tumor-suppressor loci. Br J Cancer 73: 420–423, 1996Google Scholar
  198. 198.
    Barboule N, Mazars P, Baldin V, Vidal S, Jozan S, Martel P, Valette A: Expression of p21(wafl/cip1) is heterogeneous and unrelated to proliferation index in human ovarian-careinoma. Int J Cancer 63: 611–615, 1995Google Scholar
  199. 199.
    Hatta Y, Hirama T, Takeuchi S, Lee E, Pham E, Miller CW, Strohmeyer T, Wilczynski SP, Melmed S, Koeffler HP: Alterations of the p16 (mts1) gene in testicular, ovarian, and endometrial malignancies. J Urol 154: 1954–1957, 1995Google Scholar
  200. 200.
    Rodabaugh KJ, Biggs RB, Qureshi JA, Barrett AJ, Welch WR, Bell DA, Berkowitz RS, Mok SC: Detailed deletion mapping of chromosome 9p and p16 gene alterations in human borderline and invasive epithelial ovarian-tumors. Oncogene 11: 1249–1254, 1995Google Scholar
  201. 201.
    Tavassoli M, Steingrimsdottir H, Picree E, Jiang X, Alagoz M, Farzanch F, Campbell IG: Loss of heterozygosity on chromosome 5q in ovarian-cancer is frequently accompanied by tp53 mutation and identifics a tumor-suppressor gene locus at 5q13.1–21. Br J Cancer 74: 115–119, 1996Google Scholar
  202. 202.
    Tangir J, Loughridge NS, Berkowitz RS, Muto MG, Bell DA, Welch WR, Mok SC: Frequent microsatellite instability in epithelial borderline ovarian-tumors. Cancer Res 56: 2501–2505, 1996Google Scholar
  203. 203.
    Fujita M, Enomoto T, Yoshino K, Nomura T, Buzard GS, Inoue M, Okudaira Y: Microsatellite instability and alterations in the hmsh2 gene in human ovarian-cancer. Int J Cancer 64: 361–366, 1995Google Scholar
  204. 204.
    Orth K, Hung J, Gazdar A, Bowcock A, Mathis JM, Sambrook J: Genetic instability in human ovarian-cancer cell-lines. Proc Natl Acad Sci USA 91: 9495–9499, 1994Google Scholar
  205. 205.
    Park TW, Felix JC, Wright TC: X-chromosome inactivation and microsatellite instability in early and advanced bilateral ovarian carcinomas. Cancer Res 55: 4793–4796, 1995Google Scholar
  206. 206.
    Drummond JT, Anthoney A, Brown R, Modrich P: Cisplatin and adriamyein resistance are associated with mutl-alpha and mismatch repair deficiency in an ovarian tumor-cell line. J Biol Chem 271: 19645–19648, 1996Google Scholar
  207. 207.
    Aebi S, Kurdihaidar B, Gordon R, Cenni B, Zheng H, Fink D, Christen RD, Boland CR, Koi M, Fishel R, Howell SB: Loss of DNA mismatch repair in acquired-resistance to cisplatin. Cancer Res 56: 3087–3090, 1996Google Scholar
  208. 208.
    Mello JA, Acharya S, Fishel R, Essigmann JM: The mismatch repair protein hmsh2 binds selectively to DNA-adducts of the anticancer drug cisplatin. Chem Biol 3: 579–589, 1996Google Scholar
  209. 209.
    Lastowska MA, Lillington DM, Shelling AN, Cooke I, Gibbons B, Young BD, Ganesan TS: Fluorescence in situ hybridisation analysis using cosmid probes to define chromosome 6q abnormalities in ovarian carcinoma cell lines. Cancer Genet Cytogenet 77: 99–105, 1994Google Scholar
  210. 201.
    Cooke IE, Cox SA, Shelling AN, Lemeuth VG, Spurr NK, Ganesan TS: An integrated genetic-map of chromosome-6. Mamm Genome 7: 157–159, 1996Google Scholar
  211. 211.
    Cooke IE, Shelling AN, Lemeuth VG, Charnock FML, Ganesan TS: Allele loss on chromosome arm 6q and fine mapping of the region at 6q27 in epithelial ovarian-cancer. Genes Chromosomes Cancer 15: 223–233, 1996Google Scholar
  212. 212.
    Orphanos V, McGown G, Hey Y, Thorncroft M, Santibanez KM, Russell SE, Hickey I, Atkinson RJ, Boyle JM: Allelie imbalance of chromosome 6q in ovarian tumours. Br J Cancer 71: 666–669, 1995Google Scholar
  213. 213.
    Rao BR, Slotman BJ: Endocrine factors in common epithelial ovarian cancer. Endocr Rev 12: 14–26, 1991Google Scholar
  214. 214.
    Trapani A: Estrogen receptors (ER) and progesterone receptors (PgR) in ovarian cancer. Minerva Ginecol 44: 307–312, 1992Google Scholar
  215. 215.
    Kuhnel R, de GJ, Rao BR, Stolk JG: Androgen receptor predominance in human ovarian carcinoma. J Steroid Biochem 26: 393–397, 1987Google Scholar
  216. 216.
    Kuhnel R, Delemarre JF, Rao BR, Stolk JG: Correlation of multiple steroid receptors with histological type and grade in human ovarian cancer. Int J Gynecol Pathol 6: 248–256, 1987Google Scholar
  217. 217.
    Geisler JP, Wiemann MC, Miller GA, Zhou Z, Geisler HE: Estrogen and progesterone receptors in malignant mixed mesodermal tumors of the ovary. J Surg Oncol 59: 45–47, 1995Google Scholar
  218. 218.
    Friedlander ML, Quinn MA, Fortune D, Foo MS, Toppila M, Hudson CN, Russcll P: The relationship of steroid ro ceptor expression to nuclear DNA distribution and clinicopathological characteristics in epithelial ovarian tumors. Gynecol Oncol 32: 184–190, 1989.Google Scholar
  219. 219.
    Harding M, Cowan S, Hole D, Cassidy L, Kitchener H, Davis J, Leake R: Estrogen and progesterone receptors in ovarian cancer. Cancer 65: 486–491, 1990Google Scholar
  220. 220.
    Sevelda P, Denison U, Schemper M, Spona J, Vavra N, Salzer H: Oestrogen and progesterone receptor content as a prognostic factor in advanced epithelial ovarian carcinoma. Br J Obstet Gynaecol 97: 706–712, 1990Google Scholar
  221. 221.
    Slotman BJ, Baak JP, Rao BR: Correlation between nuclear DNA content and steroid receptor status in ovarian cancer. Eur J Obstet Gynecol Reprod Biol 38: 221–227, 1991Google Scholar
  222. 222.
    Kieback DG, McCamant SK, Press MF, Atkinson EN, Gallager HS, Edwards CL, Hajek RA, Jones LA: Improved prediction of survival in advanced adenocarcinoma of the ovary by immunocytochemical analysis and the composition adjusted receptor level of the estrogen receptor. Cancer Res 53: 5188–5192, 1993Google Scholar
  223. 223.
    Kiehack DG, Press ME, Atkinson EN, Edwards GL, Mobus VJ, Runnebaum IB, Kreienberg R, Jones LA: Prognostic significance of estrogen receptor expression in ovarian cancer. Immunoreactive Score (IRS) vs. Composition Adjusted Receptor Level (CARL). Anticancer Res 13: 2489–2496, 1993Google Scholar
  224. 224.
    Langdon SP, Crew AJ, Ritchie AA, Muir M, Wakcling A, Smyth JF, Miller WR: Growth inhibition of ocstrogen receptor-positive human ovarian carcinoma by anti-oestrogens in vitro and in a xenograft model. Eur J Cancer 30A: 682–686, 1994Google Scholar
  225. 225.
    Hatch KD, Beccham JB, Blessing JA, Creasman WT: Responsiveness of patients with advanced ovarian carcinoma to tamoxifen. A Gynecologic Oncology Group study of second-line therapy in 105 patients. Cancer 68: 269–271, 1991Google Scholar
  226. 226.
    Gronroos M, Kangas L, Macnpaa J, Vanharanta R, Nieminon AL, Johansson R: Steroid receptors and response of ovarian cancer to hormones in vitro. Br J Obstet Gynaecol 91: 472–478, 1984Google Scholar
  227. 227.
    Slotman BJ, Rao BR: Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy. Anticancer Res 8: 417–434, 1988Google Scholar
  228. 228.
    Slotman BJ, Nauta JJ, Rao BR: Survival of patients with ovarian cancer. Apart from stage and grade, tumour progesterone receptor content is a prognostic indicator. Cancer 66: 740–744, 1990Google Scholar
  229. 229.
    Rao BR, Slotman BI: Action and counter-action of hormones in human ovarian cancer. Anticancer Res 9: 1005–1007, 1989Google Scholar
  230. 230.
    Tumolo S, Rao BR, van der Burg M, Guastalia JP, Renard J, Vermorken JB: Phase II trial of flutamide in advanced ovarian cancer: an EORTC Gynaecological Cancer Cooperative Group study. Eur J Cancer 30A: 911–914, 1994Google Scholar
  231. 231.
    Schally AV, Comaru SA, Redding TW: Antitumor effects of analogs of hypothalamic hormones in endocrine de pendent cancers. Proc Soc Exp Biol Med 175: 259–281, 1984Google Scholar
  232. 232.
    Schally AV, Srkalovic G, Szende B, Redding TW, Janaky T, Juhasz A, Korkut E, Cai RZ, Szepeshazi K, Radulovie S, Bokser L, Groot K, Scrfozo P, Comaruschally AM: Antitumor effects of analogs of LH-RH and somatostatin: experimental and clinical studies. J Steroid Biochem Mol Biol 37: 1061–1067, 1990Google Scholar
  233. 233.
    Emons G, Schally AV: The use of luteinizing-hormone-releasing hormone agonists and antagonists in gynecological cancers. Hum Reprod 9: 1364–1379, 1994Google Scholar
  234. 234.
    Thompson MA, Adclson MD, Kaufman LM: Lupron relards proliferation of ovarian epithelial tumor cells cultured in serum-free medium. J Clin Endocrinol Metab 72: 13036–1041, 1991Google Scholar
  235. 235.
    Yano T, Pinski J, Halmos G, Szepeshazi K, Groot K, Schally AV: Inhibition of growth of OV-1063 human epithelial ovarian cancer xenografts in nude mice by treatment with luteinizing hormone-releasing hormone antagonist SB-75. Proc Natl Acad Sci USA 91: 7090–7094, 1994Google Scholar
  236. 236.
    Yano T, Pinski J, Radulovic S, Schally AV: Inhibition of human epithelial ovarian cancer cell growth in vitro by agonistic and antagonistic analogues of luteinizing hormone-releasing hormone. Proc Natl Acad Sci USA 91: 1701–1705. 1994Google Scholar
  237. 237.
    Takagi H, Imai A, Furui T, Horibe S, Fuscya T, Tamaya T: Evidence for tight coupling of gonadotropin-releasing hormone receptors to phosphatidylinositol kinase in plasma membrane from ovarian careinomas. Gynecol Oncol 58: 110–115, 1995Google Scholar
  238. 238.
    Ron IG, Wigler N, Merimsky O, Inbar MJ, Chaitchik S: A phase-II trial of d-trp-6-Ihrh (decapeptyl) in pretreated patients with advanced epithelial ovarian-cancer. Cancer Invest 13: 272–275, 1995Google Scholar
  239. 239.
    Burger CW, Prinssen HM, Kenemans P: Lhrh agonist treatment of breast-cancer and gynecological malignancies — a review. Eur J Obstet Gynecol Reprod Biol 67: 27–33, 1996Google Scholar
  240. 240.
    Srkalovic G, Cai RZ, Schally AV: Evaluation of receptors for somatostatin in various tumors using different analogs. J Clin Endocrinol Metab 70: 661–669, 1990Google Scholar
  241. 241.
    Reubi JC, Horisberger U, Klijn JG, Foekens JA: Somatostatin receptors in differentiated ovarian tumors. Am J Pathol 138: 1267–1272, 1991Google Scholar
  242. 242.
    Reubi JC, Schaer JC, Waser B, Mengod G: Expression and localisation of somatostatin receptor sstr1, sstr2, sstr3 messenger mRNAs in primary human tumours using insitu hybridisation. Cancer Research 54: 3455–3459, 1994Google Scholar
  243. 243.
    Fayers PM, Rustin G, Wood R, Nelstrop A, Leonard RCF, Wilkinson P, Cruickshank D, McAllister EJ, Redman CWE, Parker D: The prognostic value of serum ca-125 in patients with advanced ovarian-carcinoma — an analysis of 573 patients by the medical-research-council working party on gynecological cancer. Int J Gynecol Cancer 3: 285–292, 1993Google Scholar
  244. 244.
    Gadducci A, Zola P, Landoni F, Maggino T, Sartori E, Bergamino T, Cristofani R: Serum half-life of ca-125 during early chemotherapy as an independent prognostic variable for patients with advanced epithelial ovarian-cancer — results of a multicentre italian study. Gynecol Oncol 58: 42–47, 1995Google Scholar
  245. 245.
    Geisler JP, Miller GA, Lee TH, harwood RM, Wiemann MC, Geisler HE: Relationship of preoperative serum ca-125 to survival in epithelial ovarian-carcinoma. J Reprod Med 41: 140–142, 1996Google Scholar
  246. 246.
    Maikman M: Ca-125 — an involving role in the management of ovarian-cancer. J Clin Oncol 14: 1411–1412, 1996Google Scholar
  247. 247.
    Nagele F, Kurz C, Speiser P, Vavra N, Sevelda P: Ca-125 as a prognostic factor for survival in patients with figo stage-i epithelial ovarian-cancer — preliminary results. Geburtshilfe Frauenheilkd 56: 79–82, 1996Google Scholar
  248. 248.
    Rustin GJS, Nelstrop AE, McClean P, Brady MF, McGuire WP, Hoskins WJ, Mitchell H, Lambert HE: Defining response of ovarian-carcinoma to initial chemotherapy according to serum ca-125. J Clin Oncol 14: 1545–1551, 1996Google Scholar
  249. 249.
    Yedema CA, Kenemans P, Voorhorst F, Bon G, Schijf C, Beex L, Verstraeten A, Hilgers J, Vermorken J: Ca-125 half-life in ovarian-cancer — a multivariate survival analysis. Br J Cancer 67: 1361–1367, 1993Google Scholar
  250. 250.
    Nagele F, Petru E, Medl M, Kainz C, Graf AH, Sevelda P: Preoperative ca-125 — an independent prognostic factor in patents with stage-1 epithelial ovarian-cancer. Obstet Gynecol 86: 259–264, 1995Google Scholar
  251. 251.
    Ward BG, McGuckin MA, Ramm LE, Coglan M, Sanderson B, Tripcony L, Free KE: The management of ovarian-carcinoma is improved by the use of cancer-associated serum antigen and ca-125 assays. Cancer 71: 430–438, 1993Google Scholar
  252. 252.
    Matzuk MM, Fincgold MJ, Su JG, Hsuceh AJ, Bradley A: Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360: 313–319, 1992Google Scholar
  253. 253.
    Hillier SG: Regulatory functions for inhibin and activin in human ovaries. J Endocrinol 131: 171–175, 1991Google Scholar
  254. 254.
    Lappohn RE, Burger HG, Bouma J, Bangah M, Krans M, de Bruijn H: Inhibin as a marker for granulosa-cell tumors. N Engl J Med 321: 790–793, 1989Google Scholar
  255. 255.
    Healy DL, Burger HG, Mamers P, Jobling T, Bangah M, Quinn M, Grant P, Day AJ, Rome R, Campbell JJ: Elevated serum inhibin concentrations in postmenopausal women with ovarian tumors. N Engl J Med 329: 1539–1542, 1993Google Scholar
  256. 256.
    Groome NP, Illingworth PJ, Obrien M, Cooke I, Ganesan TS, Baird DT, McNeilly AS: Detection of dimeric inhibin throughout the human menstrual-cycle by 2-site cnzymc-immunoassay. Clin Endocrinol 40: 717–723, 1994Google Scholar
  257. 257.
    Cooke I, O'Brien M, Charnock FM, Groome N, Ganesan TS: Inhibin as a marker for ovarian cancer. Br J Cancer 71: 1046–1050, 1995Google Scholar
  258. 258.
    Burger HG, Robertson DM, Cahir N, P. M, Healy DL, Jobling T, Groome N: Characterisation of inhibin immunoreactivity in post-menopausal women with ovarian tumours. Clin Endocrinol 44: 413–418, 1996Google Scholar
  259. 259.
    Gurusinghe CJ, Healy DL, Jobling T, Mamers P, Burger HG: Inhibin and activin are demonstrable by immunohistochemistry in ovarian tumor tissue. Gynecol Oncol 57: 27–32, 1995Google Scholar
  260. 260.
    Arora DS, Cooke IE, Ganesan TS, Ramsdale J, Manek S, Charnock FML, Groome NP, Wells M: Immunobistochemical expression of inhibin/activin subunits in epithelial and granulosa cell tumours of the ovary. J Path 1996, in pressGoogle Scholar
  261. 261.
    Giatromanolaki A, Koukourakis M, Obyrne K, Fox S, Whitehouse R, Talbot DC, Harris AL, Gatter KC: Prognostic value of angiogenesis in operable non-small-cell lung-cancer. J Pathol 179: 80–88, 1996Google Scholar
  262. 262.
    Gasparini G, Bonoldi E, Viale G, Verderio P, Boracchi P, Panizzoni GA, Radaelli U, Dibacco A, Guglielmi RB, Bevilacqua P: Prognostic and predictive value of tumor angiogenesis in ovarian carcinomas. Int J Cancer 69: 205–211, 1996Google Scholar
  263. 263.
    Hollingsworth HC, Kohn EC, Steinberg SM, Rothenberg ML, Merino MJ: Tumor angiogenesis in advanced stage ovarian carcinoma. Am J Pathol 147: 33–41, 1995Google Scholar
  264. 264.
    Cannistra SA, Ottensmeier C, Niloff J, Orla B, Dicarlo J: Expression and function of beta-1 and alpha-v-beta-3 integrins in ovarian-cancer. Gynecol Oncol 58: 216–225, 1995Google Scholar
  265. 265.
    Cannistra SA, Abujawdeh G, Niloff J, Strobel T, Swanson L, Andersen J, Ottensmeier C: CD44 variant expression is a common feature of epithelial ovarian-cancer — lack of association with standard prognostic factors. J Clin Oncol 13: 1912–1921, 1995Google Scholar
  266. 266.
    Scambia G, Ferrandina G, Marone M, Panici PB, Giannitelli C, Piantelli M, Leone A, Mancuso S: Nm23 in ovarian cancer — correlation with clinical outcome and other clinicopathological and biochemical prognostic parameters, J Clin Oncol 14: 334–342, 1996Google Scholar
  267. 267.
    Schmalfeldt B, Kuhn W, Reuning U, Pache L, Dettmar P, Schmitt M, Janicke F, Hofler H, Graeff H: Primary tumor and metastasis in ovarian-cancer differ in their content of urokinase-type plasminogen-activator, its receptor, and inhibitors type-1 and type-2. Cancer Res 55: 3958–3963, 1995Google Scholar
  268. 268.
    Young TN, Rodriguez GC, Rinchart AR, Bast RC, Pizzo SV, Stack MS: Characterization of gelatinases linked to extracellular-matrix invasion in ovarian adenocarcinoma-purification of matrix metalloproteinase-2. Gynecol Oncol 62: 89–99, 1996Google Scholar

Copyright information

© Kluwer Academic Publishers 1997

Authors and Affiliations

  • Roy M.T. Katso
    • 1
  • Sanjiv Manek
    • 2
  • Ken O'Byrne
    • 1
  • Martin P. Playford
    • 1
  • Valerie Le Meuth
    • 1
  • Trivadi S. Ganesan
    • 1
  1. 1.ICRF Molecular Oncology LaboratoriesInstitute of Molecular Medicine, HeadingtonOxfordUK
  2. 2.Department of Cellular PathologyJohn Radcliffe Hospital, HeadingtonOxfordUK

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