Skip to main content
SpringerLink
Log in

Molecular Markers in Epithelial Ovarian Cancer

  • Chapter
Molecular Pathology of Gynecologic Cancer

Part of the book series: Current Clinical Oncology ((CCO))

  • 970 Accesses

Abstract

More than 50% of the women diagnosed with epithelial ovarian cancer will succumb to their disease. This high death rate is because of two substantial clinical problems:

  1. 1.

    A typically late detection of the disease.

  2. 2.

    The common resistance of ovarian tumors to current therapeutic strategies.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 89.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 119.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Fishman DA, Bozorgi K. The scientific basis of early detection of epithelial ovarian cancer: the National Ovarian Cancer Early Detection Program (NOCEDP). Cancer Treat Res 2002; 107: 3–28.

    PubMed  CAS  Google Scholar 

  2. Jacobs IJ, Qram DH, Bast RC Jr. Strategies for improving the specificity of screening for ovarian cancer with tumor-associated antigens CA 125, CA 15-3, and TAG 72.3. Obstet Gynecol 1992; 80 (3 Pt 1): 396–399.

    PubMed  CAS  Google Scholar 

  3. Berek JS, Bast RC Jr. Ovarian cancer screening. The use of serial complementary tumor markers to improve sensitivity and specificity for early detection. Cancer 1995; 76(Suppl 10): 2092–2096.

    Article  PubMed  CAS  Google Scholar 

  4. Bast RC Jr, Feeney M, Lazarus H, Nadler LM, Colvin RB, Knapp RC. Reactivity of a monoclonal antibody with human ovarian carcinoma. J Clin Invest 1981; 68: 1331–1337.

    PubMed  Google Scholar 

  5. Bast RC Jr, Klug TL, St John E, et al. A radioimmunoassay using a monoclonal antibody to monitor the course of epithelial ovarian cancer. N Engl J Med 1983; 309(15): 883–887.

    Article  PubMed  Google Scholar 

  6. Zurawski VR Jr, Orjaseter H, Andersen A, Jellum E. Elevated serum CA 125 levels prior to diagnosis of ovarian neoplasia: relevance for early detection of ovarian cancer. Int J Cancer 1988; 42(5): 677–680.

    Article  PubMed  Google Scholar 

  7. Rubin SC, Hoskins WJ, Hakes TB, et al. Serum CA 125 levels and surgical findings in patients undergoing secondary operations for epithelial ovarian cancer. Am J Obstet Gynecol 1989; 160(3): 667–671.

    PubMed  CAS  Google Scholar 

  8. Jacobs I, Bast RC Jr. The CA 125 tumour-associated antigen: a review of the literature. Hum Reprod 1989; 4(1): 1–12.

    PubMed  CAS  Google Scholar 

  9. Jacobs I, Davies AP, Bridges J, et al. Prevalence screening for ovarian cancer in postmenopausal women by CA 125 measurement and ultrasonography. Bmj 1993; 306(6884): 1030–1034.

    Article  PubMed  CAS  Google Scholar 

  10. Zurawski VR Jr, Sjovall K, Schoenfeld DA, et al. Prospective evaluation of serum CA 125 levels in a normal population, phase I: the specificities of single and serial determinations in testing for ovarian cancer. Gynecol Oncol 1990; 36(3): 299–305.

    Article  PubMed  Google Scholar 

  11. Einhorn N, Sjovall K, Knapp RC, et al. Prospective evaluation of serum CA 125 levels for early detection of ovarian cancer. Obstet Gynecol 1992; 80(1): 14–18.

    PubMed  CAS  Google Scholar 

  12. Woolas RP, Oram DH, Jeyarajah AR, Bast RC, Jacobs IJ. Ovarian cancer identified through screening with serum markers but not by pelvic imaging. Int J Gynecol Cancer 1999; 9(6): 497–501.

    Article  PubMed  Google Scholar 

  13. Bast RC, Xu FJ, Yu YH, Barnhill S, Zhang Z, Mills GB. CA 125: The past and the future. Int J Biol Markers 1998; 13: 179–187.

    PubMed  CAS  Google Scholar 

  14. Wang K, Gan L, Jeffery E, et al. Monitoring gene expression profile changes in ovarian carcinomas using cDNA microarray. Gene 1999; 229: 101–108.

    Article  PubMed  CAS  Google Scholar 

  15. Schummer M, Ng VLV, Baumgarner RE, et al. Comparative hybridization of an array of 21 500 ovarian cDNAs for the discovery of genes overexpressed in ovarian carcinomas. Gene 1999; 238: 375–385.

    Article  PubMed  CAS  Google Scholar 

  16. Hough CD, Sherman-Baust CA, Pizer ES, et al. Large-Scale Serial Analysis of Gene Expression Reveals Genes Differentially Expressed in Ovarian Cancer. Cancer Res 2000; 60: 6281–6287.

    PubMed  CAS  Google Scholar 

  17. Hellstrom I, Raycraft J, Hayden-Ledbetter M, et al. The HE4 (WFDC2) Protein Is a Biomarker for Ovarian Carcinoma. Cancer Res 2003; 63: 3695–3700.

    PubMed  Google Scholar 

  18. Urban N, McIntosh MW, Andersen M, Karlan BY. Ovarian cancer screening. Hematol Oncol Clin North Am 2003; 17(4): 989–1005, ix.

    Article  PubMed  Google Scholar 

  19. Yousef GM, Diamandis EP. The new human tissue kallikrein gene family: structure, function, and association to disease. Endocr Rev 2001; 22(2): 184–204.

    Article  PubMed  CAS  Google Scholar 

  20. Diamandis EP, Scorilas A, Fracchioli S, et al. Human kallikrein 6 (hK6): a new potential serum biomarker for diagnosis and prognosis of ovarian carcinoma. J Clin Oncol 2003; 21(6): 1035–1043.

    Article  PubMed  CAS  Google Scholar 

  21. Luo LY, Katsaros D, Scorilas A, et al. The serum concentration of human kallikrein 10 represents a novel biomarker for ovarian cancer diagnosis and prognosis. Cancer Res 2003; 63(4): 807–811.

    PubMed  CAS  Google Scholar 

  22. Diamandis EP, Okui A, Mitsui S, et al. Human kallikrein 11: a new biomarker of prostate and ovarian carcinoma. Cancer Res 2002; 62(1): 295–300.

    PubMed  CAS  Google Scholar 

  23. Petricoin EF, Ardekani AM, Hitt BA, et al. Use of proteomic patterns in serum to identify ovarian cancer. Lancet 2002; 359(9306): 572–577.

    Article  PubMed  CAS  Google Scholar 

  24. Zhang Z, Bast RC Jr, Yu Y, et al. Three biomarkers identified from serum proteomic analysis for the detection of early stage ovarian cancer. Cancer Res 2004; 64(16): 5882–5890.

    Article  PubMed  CAS  Google Scholar 

  25. Ono K, Tanaka T, Tsunoda T, et al. Identification by cDNA microarray of genes involved in ovarian carcinogenesis. Cancer Res 2000; 60(18): 5007–5011.

    PubMed  CAS  Google Scholar 

  26. Martoglio AM, Tom BD, Starkey M, Corps AN, Charnock-Jones DS, Smith SK. Changes in tumorigenesis-and angiogenesis-related gene transcript abundance profiles in ovarian cancer detected by tailored high density cDNA arrays. Mol Med 2000; 6(9): 750–765.

    PubMed  CAS  Google Scholar 

  27. Ismail RS, Baldwin RL, Fang J, et al. Differential gene expression between normal and tumorderived ovarian epithelial cells. Cancer Res 2000; 60(23): 6744–6749.

    PubMed  CAS  Google Scholar 

  28. Hough CD, Cho KR, Zonderman AB, Schwartz DR, Morin PJ. Coordinately up-regulated genes in ovarian cancer. Cancer Res 2001; 61(10): 3869–3876.

    PubMed  CAS  Google Scholar 

  29. Shridhar V, Lee J, Pandita A, et al. Genetic analysis of earlyversus late-stage ovarian tumors. Cancer Res 2001; 61(15): 5895–5904.

    PubMed  CAS  Google Scholar 

  30. Wong KK, Cheng RS, Mok SC. Identification of differentially expressed genes from ovarian cancer cells by MICROMAX cDNA microarray system. Biotechniques 2001; 30(3): 670–675.

    PubMed  CAS  Google Scholar 

  31. Tonin PN, Hudson TJ, Rodier F, et al. Microarray analysis of gene expression mirrors the biology of an ovarian cancer model. Oncogene 2001; 20(45): 6617–6626.

    Article  PubMed  CAS  Google Scholar 

  32. Welsh JB, Zarrinkar PP, Sapinoso LM, et al. Analysis of gene expression profiles in normal and neoplastic ovarian tissue samples identifies candidate molecular markers of epithelial ovarian cancer. Proc Natl Acad Sci USA 2001; 98(3): 1176–1181.

    Article  PubMed  CAS  Google Scholar 

  33. Schwartz DR, Kardia SL, Shedden KA, et al. Gene expression in ovarian cancer reflects both morphology and biological behavior, distinguishing clear cell from other poorprognosis ovarian carcinomas. Cancer Res 2002; 62(16): 4722–4729.

    PubMed  CAS  Google Scholar 

  34. Matei D, Graeber TG, Baldwin RL, Karlan BY, Rao J, Chang DD. Gene expression in epithelial ovarian carcinoma. Oncogene 2002; 21(41): 6289–6298.

    Article  PubMed  CAS  Google Scholar 

  35. Bayani J, Brenton JD, Macgregor PF, et al. Parallel analysis of sporadic primary ovarian carcinomas by spectral karyotyping, comparative genomic hybridization, and expression microarrays. Cancer Res 2002; 62(12): 3466–3476.

    PubMed  CAS  Google Scholar 

  36. Sawiris GP, Sherman-Baust CA, Becker KG, Cheadle C, Teichberg D, Morin PJ. Development of a highly specialized cDNA array for the study and diagnosis of epithelial ovarian cancer. Cancer Res 2002; 62(10): 2923–2928.

    PubMed  CAS  Google Scholar 

  37. Shridhar V, Sen A, Chien J, et al. Identification of underexpressed genes in early-and late-stage primary ovarian tumors by suppression subtraction hybridization. Cancer Res 2002; 62(1): 262–270.

    PubMed  CAS  Google Scholar 

  38. Schaner ME, Ross DT, Ciaravino G, et al. Gene expression patterns in ovarian carcinomas. Mol Biol Cell 2003; 14(11): 4376–4386.

    Article  PubMed  CAS  Google Scholar 

  39. Shvartsman HS, Lu KH, Lee J, et al. Overexpression of kallikrein 10 in epithelial ovarian carcinomas. Gynecol Oncol 2003; 90(1): 44–50.

    Article  PubMed  CAS  Google Scholar 

  40. Jazaeri AA, Lu K, Schmandt R, et al. Molecular determinants of tumor differentiation in papillary serous ovarian carcinoma. Mol Carcinog 2003; 36(2): 53–59.

    Article  PubMed  CAS  Google Scholar 

  41. Spentzos D, Levine DA, Ramoni MF, et al. Gene expression signature with independent prognostic significance in epithelial ovarian cancer. J Clin Oncol 2004; 22(23): 4648–4658.

    Article  Google Scholar 

  42. Donninger H, Bonome T, Radonovich M, et al. Whole genome expression profiling of advance stage papillary serous ovarian cancer reveals activated pathways. Oncogene 2004; 23(49): 8065–8077.

    Article  PubMed  CAS  Google Scholar 

  43. Santin AD, Zhan F, Bellone S, et al. Gene expression profiles in primary ovarian serous papillary tumors and normal ovarian epithelium: Identification of candidate molecular markers for ovarian cancer diagnosis and therapy. Int J Cancer 2004; 112(1): 14–25.

    Article  PubMed  CAS  Google Scholar 

  44. Adib TR, Henderson S, Perrett C, et al. Predicting biomarkers for ovarian cancer using gene-expression microarrays. Br J Cancer 2004; 90(3): 686–692.

    Article  PubMed  CAS  Google Scholar 

  45. Lu KH, Patterson AP, Wang L, et al. Selection of potential markers for epithelial ovarian cancer with gene expression arrays and recursive descent partition analysis. Clin Cancer Res 2004; 10(10): 3291–3300.

    Article  PubMed  CAS  Google Scholar 

  46. Heinzelmann-Schwarz VA, Gardiner-Garden M, Henshall SM, et al. Overexpression of the cell adhesion molecules DDR1, Claudin 3, and Ep-CAM in metaplastic ovarian epithelium and ovarian cancer. Clin Cancer Res 2004; 10(13): 4427–4436.

    Article  PubMed  CAS  Google Scholar 

  47. Hofseth LJ, Hussain SP, Harris CC. p53: 25 years after its discovery. Trends Pharmacol Sci 2004; 25(4): 177–181.

    Article  PubMed  CAS  Google Scholar 

  48. Takahashi T, Nau MM, Chiba I, et al. p53: a frequent target for genetic abnormalities in lung cancer. Science 1989; 246(4929): 491–494.

    Article  PubMed  CAS  Google Scholar 

  49. Nigro JM, Baker SJ, Preisinger AC, et al. Mutations in the p53 gene occur in diverse human tumour types. Nature 1989; 342(6250): 705–708.

    Article  PubMed  CAS  Google Scholar 

  50. Hollstein M, Sidransky D, Vogelstein B, Harris CC. p53 mutations in human cancers. Science 1991; 253(5015): 49–53.

    Article  PubMed  CAS  Google Scholar 

  51. Kihana T, Tsuda H, Teshima S, Okada S, Matsuura S, Hirohashi S. High incidence of p53 gene mutation in human ovarian cancer and its association with nuclear accumulation of p53 protein and tumor DNA aneuploidy. Japan J Cancer Res 1992; 83(9): 978–984.

    CAS  Google Scholar 

  52. Okamoto A, Sameshima Y, Yokoyama S, et al. Frequent allelic losses and mutations of the p53 gene in human ovarian cancer. Cancer Res 1991; 51(19): 5171–5176.

    PubMed  CAS  Google Scholar 

  53. Marks JR, Davidoff AM, Kerns BJ, et al. Overexpression and mutation of p53 in epithelial ovarian cancer. Cancer Res 1991; 51(11): 2979–2984.

    PubMed  CAS  Google Scholar 

  54. Teneriello MG, Ebina M, Linnoila RI, et al. p53 and Ki-ras gene mutations in epithelial ovarian neoplasms. Cancer Res 1993; 53: 3103–3108.

    PubMed  CAS  Google Scholar 

  55. Milner BJ, Allan LA, Eccles DM, et al. p53 mutation is a common genetic event in ovarian carcinoma. Cancer Res 1993; 53: 2128–2132.

    PubMed  CAS  Google Scholar 

  56. van der Zee AG, Hollema H, Suurmeijer AJ, et al. Value of P-glycoprotein, glutathione S-transferase pi, c-erbB-2, and p53 as prognostic factors in ovarian carcinomas. J Clin Oncol 1995; 13(1): 70–78.

    PubMed  Google Scholar 

  57. Levesque MA, Katsaros D, Yu H, et al. Mutant p53 protein overexpression is associated with poor outcome in patients with well or moderately differentiated ovarian carcinoma. Cancer 1995; 75(6): 1327–1338.

    Article  PubMed  CAS  Google Scholar 

  58. Klemi PJ, Pylkkanen L, Kiilholma P, Kurvinen K, Joensuu H. p53 protein detected by immunohisto-chemistry as a prognostic factor in patients with epithelial ovarian carcinoma. Cancer 1995; 76(7): 1201–1208.

    Article  PubMed  CAS  Google Scholar 

  59. Diebold J, Baretton G, Felchner M, et al. bcl-2 expression, p53 accumulation, and apoptosis in ovarian carcinomas. Am J Clin Pathol 1996; 105(3): 341–349.

    PubMed  CAS  Google Scholar 

  60. Buttitta F, Marchetti A, Gadducci A, et al. p53 alterations are predictive of chemoresistance and aggressiveness in ovarian carcinomas: a molecular and immunohistochemical study. Br J Cancer 1997; 75(2): 230–235.

    PubMed  CAS  Google Scholar 

  61. Geisler JP, Geisler HE, Wiemann MC, Givens SS, Zhou Z, Miller GA. Quantification of p53 in epithelial ovarian cancer. Gynecol Oncol 1997; 66(3): 435–438.

    Article  PubMed  CAS  Google Scholar 

  62. Dong Y, Walsh MD, McGuckin MA, et al. Reduced expression of retinoblastoma gene product (pRB) and high expression of p53 are associated with poor prognosis in ovarian cancer. Int J Cancer 1997; 74(4): 407–415.

    Article  PubMed  CAS  Google Scholar 

  63. Anttila MA, Ji H, Juhola MT, Saarikoski SV, Syrjanen KJ. The prognostic significance of p53 expression quantitated by computerized image analysis in epithelial ovarian cancer. Int J Gynecol Pathol 1999; 18(1): 42–51.

    Article  PubMed  CAS  Google Scholar 

  64. Baekelandt M, Kristensen GB, Nesland JM, Trope CG, Holm R. Clinical significance of apoptosisrelated factors p53, Mdm2, and Bcl-2 in advanced ovarian cancer. J Clin Oncol 1999; 17: 2061–2068.

    PubMed  CAS  Google Scholar 

  65. Sood AK, Sorosky JI, Dolan M, Anderson B, Buller RE. Distant metastases in ovarian cancer: association with p53 mutations. Clin Cancer Res 1999; 5(9): 2485–2490.

    PubMed  CAS  Google Scholar 

  66. Levesque MA, Katsaros D, Massobrio M, et al. Evidence for a dose-response effect between p53 (but not p21WAFl/Cipl) protein concentrations, survival, and responsiveness in patients with epithelial ovarian cancer treated with platinum-based chemotherapy. Clin Cancer Res 2000; 6(8): 3260–3270.

    PubMed  CAS  Google Scholar 

  67. Reles A, Wen WH, Schmider A, et al. Correlation of p53 mutations with resistance to platinum-based chemotherapy and shortened survival in ovarian cancer. Clin Cancer Res 2001; 7(10): 2984–2997.

    PubMed  CAS  Google Scholar 

  68. Schuyer M, van der Burg ME, Henzen-Logmans SC, et al. Reduced expression of BAX is associated with poor prognosis in patients with epithelial ovarian cancer: a multifactorial analysis of TP53, p21, BAX and BCL-2. Br J Cancer 2001; 85(9): 1359–1367.

    Article  PubMed  CAS  Google Scholar 

  69. Hawes D, Liu PY, Muggia FM, et al. Correlation of p53 immunostaining in primary and residual ovarian cancer at the time of positive second-look laparotomy and its prognostic role: a Southwest Oncology Group ancillary study. Gynecol Oncol 2002; 87(1): 17–23.

    Article  PubMed  CAS  Google Scholar 

  70. Skirnisdottir I, Scidal T, Gerdin E, Sorbe B. The prognostic importance of p53, bcl-2, and bax in early stage epithelial ovarian carcinoma treated with adjuvant chemotherapy. Int J Gynecol Cancer 2002; 12(3): 265–276.

    Article  PubMed  CAS  Google Scholar 

  71. Bali A, O’Brien PM, Edwards LS, Sutherland RL, Hacker NF, Henshall SM. Cyclin Dl, p53, and p21Waf 1/Cipl expression is predictive of poor clinical outcome in serous epithelial ovarian cancer. Clin Cancer Res 2004; 10(15): 5168–5177.

    Article  PubMed  CAS  Google Scholar 

  72. Nielsen JS, Jakobsen E, Holund B, Bertelsen K, Jakobsen A. Prognostic significance of p53, Her-2, and EGFR overexpression in borderline and epithelial ovarian cancer. Int J Gynecol Cancer 2004; 14(6): 1086–1096.

    Article  PubMed  CAS  Google Scholar 

  73. 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 cytometry. Gynecol Oncol 1994; 53(3): 301–306.

    Article  PubMed  CAS  Google Scholar 

  74. Herod JJ, Eliopoulos AG, Warwick J, Niedobitek G, Young LS, Kerr DJ. The prognostic significance of Bcl-2 and p53 expression in ovarian carcinoma. Cancer Res 1996; 56(9): 2178–2184.

    PubMed  CAS  Google Scholar 

  75. Werness BA, Freedman AN, Piver MS, Romero-Gutierrez M, Petrow E. Prognostic significance of p53 and p21(wafl/cipl) immunoreactivity in epithelial cancers of the ovary. Gynecol Oncol 1999; 75(3): 413–418.

    Article  PubMed  CAS  Google Scholar 

  76. Tachibana M, Watanabe J, Matsushima Y, et al. Independence of the prognostic value of tumor suppressor protein expression in ovarian adenocarcinomas: a multivariate analysis of expression of p53, retinoblastoma, and related proteins. Int J Gynecol Cancer 2003; 13(5): 598–606.

    Article  PubMed  CAS  Google Scholar 

  77. Shahin MS, Hughes JH, Sood AK, Buller RE. The prognostic significance of p53 tumor suppressor gene alterations in ovarian carcinoma. Cancer 2000; 89(9): 2006–2017.

    Article  PubMed  CAS  Google Scholar 

  78. Skomedal H, Kristensen GB, Abeler VM, Borresen-Dale AL, Trope C, Holm R. TP53 protein accumulation and gene mutation in relation to overexpression of MDM2 protein in ovarian borderline tumours and stage I carcinomas. J Pathol 1997; 181(2): 158–165.

    Article  PubMed  CAS  Google Scholar 

  79. Hartmann LC, Podratz KC, Keeney GL, et al. Prognostic significance of p53 immunostaining in epithelial ovarian cancer. J Clin Oncol 1994; 12: 64–69.

    PubMed  CAS  Google Scholar 

  80. Kohler MF, Kems BJ, Humphrey PA, Marks JR, Bast RC Jr, Berchuck A. Mutation and overexpression of p53 in early-stage epithelial ovarian cancer. Obstet Gynecol 1993; 81 (5 Pt 1): 643–650.

    PubMed  CAS  Google Scholar 

  81. Reles A, Schmider A, Press MF, et al. Immunostaining of p53 protein in ovarian carcinoma: correlation with histopathological data and clinical outcome. J Cancer Res Clin Oncol 1996; 122(8): 489–494.

    Article  PubMed  CAS  Google Scholar 

  82. Eltabbakh GH, Belinson JL, Kennedy AW, et al. p53 overexpression is not an independent prognostic factor for patients with primary ovarian epithelial cancer. Cancer 1997; 80(5): 892–898.

    Article  PubMed  CAS  Google Scholar 

  83. Fallows S, Price J, Atkinson RJ, Johnston PG, Hickey I, Russell SE. P53 mutation does not affect prognosis in ovarian epithelial malignancies. J Pathol 2001; 194(1): 68–75.

    Article  PubMed  CAS  Google Scholar 

  84. Berker B, Dunder I, Ensari A, Cengiz SD. Prognostic value of p53 accumulation in epithelial ovarian carcinomas. Arch Gynecol Obstet 2002; 266(4): 205–209.

    Article  PubMed  CAS  Google Scholar 

  85. Laframboise S, Chapman W, McLaughlin J, Andrulis IL. p53 mutations in epithelial ovarian cancers: possible role in predicting chemoresistance. Cancer J 2000; 6(5): 302–308.

    PubMed  CAS  Google Scholar 

  86. Peiro G, Diebold J, Lohrs U. CAS (cellular apoptosis susceptibility) gene expression in ovarian carcinoma: Correlation with 20ql3.2 copy number and cyclin Dl, p53, and Rb protein expression. Am J Clin Pathol 2002; 118(6): 922–929.

    Article  PubMed  CAS  Google Scholar 

  87. Kupryjanczyk J, Thor AD, Beauchamp R, et al. p53 gene mutations and protein accumulation in human ovarian cancer. Proc Natl Acad Sci USA 1993; 90(11): 4961–4965.

    Article  PubMed  CAS  Google Scholar 

  88. Rose SL, Robertson AD, Goodheart MJ, Smith BJ, De Young BR, Buller RE. The impact of p53 protein core domain structural alteration on ovarian cancer survival. Clin Cancer Res 2003; 9(11): 4139–4144.

    PubMed  CAS  Google Scholar 

  89. Plisiecka-Halasa J, Karpinska G, Szymanska T, et al. P21WAF1, P27KIP1, TP53 and C-MYC analysis in 204 ovarian carcinomas treated with platinum-based regimens. Ann Oncol 2003; 14(7): 1078–1085.

    Article  PubMed  CAS  Google Scholar 

  90. Kupryjanczyk J, Szymanska T, Madry R, et al. Evaluation of clinical significance of TP53, BCL-2, BAX and MEK1 expression in 229 ovarian carcinomas treated with platinum-based regimen. Br J Cancer 2003; 88(6): 848–854.

    Article  PubMed  CAS  Google Scholar 

  91. Sheridan E, Silcocks P, Smith J, Hancock BW, Goyns MH. P53 mutation in a series of epithelial ovarian cancers from the U.K., and its prognostic significance. Eur J Cancer 1994; 30A(11): 1701–1704.

    Article  PubMed  CAS  Google Scholar 

  92. Niwa K, Itoh M, Murase T, et al. Alteration of p53 gene in ovarian carcinoma: clinicopathological correlation and prognostic significance. Br J Cancer 1994; 70(6): 1191–1197.

    PubMed  CAS  Google Scholar 

  93. Allan LA, Campbell MK, Milner BJ, et al. The significance of p53 mutation and over-expression in ovarian prognosis. Int J Gynecol Cancer 1996; 196(6): 483–490.

    Article  Google Scholar 

  94. Smith-Sorensen B, Kaern J, Holm R, Dorum A, Trope C, Borresen-Dale AL. Therapy effect of either paclitaxel or cyclophosphamide combination treatment in patients with epithelial ovarian cancer and relation to TP53 gene status. Br J Cancer 1998; 78: 375–381.

    PubMed  CAS  Google Scholar 

  95. Havrilesky L, Darcy M, Hamdan H, et al. Prognostic significance of p53 mutation and p53 overexpression in advanced epithelial ovarian cancer: a Gynecologic Oncology Group Study. J Clin Oncol 2003; 21(20): 3814–3825.

    Article  PubMed  CAS  Google Scholar 

  96. Wang Y, Heiland A, Holm R, et al. TP53 mutations in early-stage ovarian carcinoma, relation to long-term survival. Br J Cancer 2004; 90(3): 678–685.

    Article  PubMed  CAS  Google Scholar 

  97. Marx D, Meden H, Ziemek T, Lenthe T, Kuhn W, Schauer A. Expression of the p53 tumour suppressor gene as a prognostic marker in platinum-treated patients with ovarian cancer. Eur J Cancer 1998; 34(6): 845–850.

    Article  PubMed  CAS  Google Scholar 

  98. Sengupta PS, McGown AT, Bajaj V, et al. p53 and related proteins in epithelial ovarian cancer. Eur J Cancer 2000; 36(18): 2317–2328.

    Article  PubMed  CAS  Google Scholar 

  99. Ferrandina G, Fagotti A, Salerno MG, et al. p53 overexpression is associated with cytoreduction and response to chemotherapy in ovarian cancer. Br J Cancer 1999; 81(4): 733–740.

    Article  PubMed  CAS  Google Scholar 

  100. Righetti SC, Delia Torre G, Pilotti S, et al. A comparative study of p53 gene mutations, protein accumulation, and response to cisplatin-based chemotherapy in advanced ovarian carcinoma. Cancer Res 1996; 56(4): 689–693.

    PubMed  CAS  Google Scholar 

  101. Nakayama K, Takebayashi Y, Nakayama S, et al. Prognostic value of overexpression of p53 in human ovarian carcinoma patients receiving cisplatin. Cancer Lett 2003; 192(2): 227–235.

    Article  PubMed  CAS  Google Scholar 

  102. Rohlke P, Milde-Langosch K, Weyland C, Pichlmeier U, Jonat W, Loning T. p53 is a persistent and predictive marker in advanced ovarian carcinomas: multivariate analysis including comparison with Ki67 immunoreactivity. J Cancer Res Clin Oncol 1997; 123(9): 496–501.

    Article  PubMed  CAS  Google Scholar 

  103. Lavarino C, Pilotti S, Oggionni M, et al. p53 gene status and response to platinum/paclitaxel-based chemotherapy in advanced ovarian carcinoma. J Clin Oncol 2000; 18(23): 3936–3945.

    PubMed  CAS  Google Scholar 

  104. Murray AW. Recycling the cell cycle: cyclins revisited. Cell 2004; 116(2): 221–234.

    Article  PubMed  CAS  Google Scholar 

  105. Baekelandt M, Holm R, Trope CG, Nesland JM, Kristensen GB. Lack of independent prognostic significance of p21 and p27 expression in advanced ovarian cancer: an immunohistochemical study. Clin Cancer Res 1999; 5(10): 2848–2853.

    PubMed  CAS  Google Scholar 

  106. Vassilopoulos I, Korkolopoulou P, Konstantinidou AE, et al. Evaluation of the cyclin-dependent kinase inhibitor p21Cipl in epithelial ovarian tumors of low malignant potential and adenocarcinomas. Histol Histopathol 2003; 18(3): 761–770.

    PubMed  CAS  Google Scholar 

  107. Milde-Langosch K, Hagen M, Bamberger AM, Loning T. Expression and prognostic value of the cell-cycle regulatory proteins, Rb, p16MTSl, p21WAFl, p27KIPl, cyclin E, and cyclin D2, in ovarian cancer. Int J Gynecol Pathol 2003; 22(2): 168–174.

    Article  PubMed  Google Scholar 

  108. Geisler HE, Geisler JP, Miller GA, et al. p21 and p53 in ovarian carcinoma: their combined staining is more valuable than either alone. Cancer 2001; 92(4): 781–786.

    Article  PubMed  CAS  Google Scholar 

  109. Newcomb EW, Sosnow M, Demopoulos RI, Zeleniuch-Jacquotte A, Sorich J, Speyer JL. Expression of the cell cycle inhibitor p27KIPl is a new prognostic marker associated with survival in epithelial ovarian tumors. Am J Pathol 1999; 154(1): 119–125.

    PubMed  CAS  Google Scholar 

  110. Korkolopoulou P, Vassilopoulos I, Konstantinidou AE, et al. The combined evaluation of p27Kipl and Ki-67 expression provides independent information on overall survival of ovarian carcinoma patients. Gynecol Oncol 2002; 85(3): 404–414.

    Article  PubMed  Google Scholar 

  111. Sui L, Dong Y, Ohno M, et al. Implication of malignancy and prognosis of p27(kipl), Cyclin E, and Cdk2 expression in epithelial ovarian tumors. Gynecol Oncol 2001; 83(1): 56–63.

    Article  PubMed  CAS  Google Scholar 

  112. Shigemasa K, Shiroyama Y, Sawasaki T, et al. Underexpression of cyclin-dependent kinase inhibitor p27 is associated with poor prognosis in serous ovarian carcinomas. Int J Oncol 2001; 18(5): 953–958.

    PubMed  CAS  Google Scholar 

  113. Masciullo V, Ferrandina G, Pucci B, et al. p27Kipl expression is associated with clinical outcome in advanced epithelial ovarian cancer: multivariate analysis. Clin Cancer Res 2000; 6(12): 4816–4822.

    PubMed  CAS  Google Scholar 

  114. Kusume T, Tsuda H, Kawabata M, et al. The pl6-cyclin Dl/CDK4-pRb pathway and clinical outcome in epithelial ovarian cancer. Clin Cancer Res 1999; 5(12): 4152–4157.

    PubMed  CAS  Google Scholar 

  115. Sui L, Dong Y, Ohno M, et al. Inverse expression of Cdk4 and pl6 in epithelial ovarian tumors. Gynecol Oncol 2000; 79(2): 230–237.

    Article  PubMed  CAS  Google Scholar 

  116. Katsaros D, Cho W, Singal R, et al. Methylation of tumor suppressor gene pl6 and prognosis of epithelial ovarian cancer. Gynecol Oncol 2004; 94(3): 685–692.

    Article  PubMed  CAS  Google Scholar 

  117. Kudoh K, Ichikawa Y, Yoshida S, et al. Inactivation of pl6/CDKN2 and pl5/MTS2 is associated with prognosis and response to chemotherapy in ovarian cancer. Int J Cancer 2002; 99(4): 579–582.

    Article  PubMed  CAS  Google Scholar 

  118. Dong Y Walsh MD, McGuckin MA, et al. Increased expression of cyclin-dependent kinase inhibitor 2 (CDKN2A) gene product P16INK4A in ovarian cancer is associated with progression and unfavourable prognosis. Int J Cancer 1997; 74(1): 57–63.

    Article  PubMed  CAS  Google Scholar 

  119. Rosenberg E, Demopoulos RI, Zeleniuch-Jacquotte A, et al. Expression of cell cycle regulators p57(KIP2), cyclin Dl, and cyclin E in epithelial ovarian tumors and survival. Hum Pathol 2001; 32(8): 808–813.

    Article  PubMed  CAS  Google Scholar 

  120. Sui L, Dong Y, Ohno M, Watanabe Y Sugimoto K, Tokuda M. Expression of p57kip2 and its clinical relevance in epithelial ovarian tumors. Anticancer Res 2002; 22(6A): 3191–3196.

    PubMed  CAS  Google Scholar 

  121. Barbieri F, Lorenzi P, Ragni N, et al. Overexpression of cyclin Dl is associated with poor survival in epithelial ovarian cancer. Oncology 2004; 66(4): 310–315.

    Article  PubMed  CAS  Google Scholar 

  122. Diebold J, Mosinger K, Peiro G, et al. 20ql3 and cyclin Dl in ovarian carcinomas. Analysis by fluorescence in situ hybridization. J Pathol 2000; 190(5): 564–571.

    Article  PubMed  CAS  Google Scholar 

  123. Dhar KK, Branigan K, Parkes J, et al. Expression and subcellular localization of cyclin Dl protein in epithelial ovarian tumour cells. Br J Cancer 1999; 81: 1174–1181.

    Article  PubMed  CAS  Google Scholar 

  124. Farley J, Smith LM, Darcy KM, et al. Cyclin E expression is a significant predictor of survival in advanced, suboptimally debulked ovarian epithelial cancers: a Gynecologic Oncology Group study. Cancer Res 2003; 63(6): 1235–1241.

    PubMed  CAS  Google Scholar 

  125. Konstantinidou AE, Korkolopoulou P, Vassilopoulos I, et al. Reduced retinoblastoma gene protein to Ki-67 ratio is an adverse prognostic indicator for ovarian adenocarcinoma patients. Gynecol Oncol 2003; 88(3): 369–378.

    Article  PubMed  CAS  Google Scholar 

  126. Lohmann CM, League AA, Clark WS, Lawson D, DeRose PB, Cohen C. Bcl-2: bax and bcl-2: Bcl-x ratios by image cytometric quantitation of immunohistochemical expression in ovarian carcinoma: correlation with prognosis. Cytometry 2000; 42(1): 61–66.

    Article  PubMed  CAS  Google Scholar 

  127. Baekelandt M, Holm R, Nesland JM, Trope CG, Kristensen GB. Expression of apoptosis-related proteins is an independent determinant of patient prognosis in advanced ovarian cancer. J Clin Oncol 2000; 18(22): 3775–3781.

    PubMed  CAS  Google Scholar 

  128. Mano Y, Kikuchi Y, Yamamoto K, et al. Bcl-2 as a predictor of chemosensitivity and prognosis in primary epithelial ovarian cancer. Eur J Cancer 1999; 35(8): 1214–1219.

    Article  PubMed  CAS  Google Scholar 

  129. Ferrandina G, Legge F, Martinelli E, et al. Survivin expression in ovarian cancer and its correlation with clinico-pathological, surgical and apoptosis-related parameters. Br J Cancer 2005.

    Google Scholar 

  130. Cohen C, Lohmann CM, Cotsonis G, Lawson D, Santoianni R. Survivin expression in ovarian carcinoma: correlation with apoptotic markers and prognosis. Mod Pathol 2003; 16(6): 574–583.

    Article  PubMed  Google Scholar 

  131. Sui L, Dong Y, Ohno M, Watanabe Y Sugimoto K, Tokuda M. Survivin expression and its correlation with cell proliferation and prognosis in epithelial ovarian tumors. Int J Oncol 2002; 21(2): 315–320.

    PubMed  CAS  Google Scholar 

  132. de Bruijn HW, van der Zee AG, Aalders JG. The value of cancer antigen 125 (CA 125) during treatment and follow-up of patients with ovarian cancer. Curr Opin Obstet Gynecol 1997; 9(1): 8–13.

    PubMed  Google Scholar 

  133. Yang G, Cai KQ, Thompson-Lanza JA, Bast RC Jr, Liu J. Inhibition of breast and ovarian tumor growth through multiple signaling pathways by using retrovirus-mediated small interfering RNA against Her-2/neu gene expression. J Biol Chem 2004; 279(6): 4339–4345.

    Article  PubMed  CAS  Google Scholar 

  134. Fajac A, Benard J, Lhomme C, et al. c-erbB2 gene amplification and protein expression in ovarian epithelial tumors: evaluation of their respective prognostic significance by multivariate analysis. Int J Cancer 1995; 64(2): 146–151.

    Article  PubMed  CAS  Google Scholar 

  135. Tanner B, Kreutz E, Weikel W, et al. Prognostic significance of c-erB-2 mRNA in ovarian carcinoma. Gynecol Oncol 1996; 62(2): 268–277.

    Article  PubMed  CAS  Google Scholar 

  136. Ross JS, Yang F, Kallakury BV, Sheehan CE, Ambros RA, Muraca PJ. HER-2/neu oncogene amplification by fluorescence in situ hybridization in epithelial tumors of the ovary. Am J Clin Pathol 1999; 111(3): 311–316.

    PubMed  CAS  Google Scholar 

  137. Riener EK, Arnold N, Kommoss F, Lauinger S, Pfisterer J. The prognostic and predictive value of immunohistochemically detected HER-2/neu overexpression in 361 patients with ovarian cancer: a multicenter study. Gynecol Oncol 2004; 95(1): 89–94.

    Article  PubMed  CAS  Google Scholar 

  138. Tanabe H, Nishii H, Sakata A, et al. Overexpression of HER-2/neu is not a risk factor in ovarian clear cell adenocarcinoma. Gynecol Oncol 2004; 94(3): 735–739.

    Article  PubMed  CAS  Google Scholar 

  139. van Dam PA, Vergote IB, Lowe DG, et al. Expression of c-erbB-2, c-myc, and c-ras oncoproteins, insulin-like growth factor receptor I, and epidermal growth factor receptor in ovarian carcinoma. J Clin Pathol 1994; 47(10): 914–919.

    Article  PubMed  Google Scholar 

  140. Lukes AS, Kohler MF, Pieper CF, et al. Multivariable analysis of DNA ploidy, p53, and HER-2/neu as prognostic factors in endometrial cancer. Cancer 1994; 73(9): 2380–2385.

    Article  PubMed  CAS  Google Scholar 

  141. Singleton TP, Perrone T, Oakley G, et al. Activation of c-erbB-2 and prognosis in ovarian carcinoma. Comparison with histologic type, grade, and stage. Cancer 1994; 73(5): 1460–1466.

    Article  PubMed  CAS  Google Scholar 

  142. Rubin SC, Finstad CL, Wong GY, Almadrones L, Plante M, Lloyd KO. Prognostic significance of HER-2/neu expression in advanced epithelial ovarian cancer: a multivariate analysis. Am J Obstet Gynecol 1993; 168 (1 Pt 1): 162–169.

    PubMed  CAS  Google Scholar 

  143. Camilleri-Broet S, Hardy-Bessard AC, Le Tourneau A, et al. HER-2 overexpression is an independent marker of poor prognosis of advanced primary ovarian carcinoma: a multicenter study of the GINECO group. Ann Oncol 2004; 15(1): 104–112.

    Article  PubMed  CAS  Google Scholar 

  144. Felip E, Del Campo JM, Rubio D, Vidal MT, Colomer R, Bermejo B. Overexpression of c-erbB-2 in epithelial ovarian cancer. Prognostic value and relationship with response to chemotherapy. Cancer 1995; 75(8): 2147–2152.

    Article  PubMed  CAS  Google Scholar 

  145. 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 1995; 21(2): 167–178.

    PubMed  CAS  Google Scholar 

  146. Pegram MD, Finn RS, Arzoo K, Beryt M, Pietras RJ, Slamon DJ. The effect of HER-2/neu overexpression on chemotherapeutic drug sensitivity in human breast and ovarian cancer cells. Oncogene 1997; 15(5): 537–547.

    Article  PubMed  CAS  Google Scholar 

  147. Agus DB, Bunn PA Jr, Franklin W, Garcia M, Ozols RF. HER-2/neu as a therapeutic target in nonsmall cell lung cancer, prostate cancer, and ovarian cancer. Semin Oncol 2000; 27(6 Suppl 11): 53–63; discussion 92-100.

    PubMed  CAS  Google Scholar 

  148. Luo LY, Katsaros D, Scorilas A, et al. Prognostic value of human kallikrein 10 expression in epithelial ovarian carcinoma. Clin Cancer Res 2001; 7(8): 2372–2379.

    PubMed  CAS  Google Scholar 

  149. Diamandis EP, Borgono CA, Scorilas A, Harbeck N, Dorn J, Schmitt M. Human kallikrein 11: an indicator of favorable prognosis in ovarian cancer patients. Clin Biochem 2004; 37(9): 823–829.

    Article  PubMed  CAS  Google Scholar 

  150. Shigemasa K, Gu L, Tanimoto H, O’Brien TJ, Ohama K. Human kallikrein gene 11 (KLK11) mRNA overexpression is associated with poor prognosis in patients with epithelial ovarian cancer. Clin Cancer Res 2004; 10(8): 2766–2770.

    Article  PubMed  CAS  Google Scholar 

  151. Borgono CA, Fracchioli S, Yousef GM, et al. Favorable prognostic value of tissue human kallikrein 11 (hKll) in patients with ovarian carcinoma. Int J Cancer 2003; 106(4): 605–610.

    Article  PubMed  CAS  Google Scholar 

  152. Scorilas A, Borgono CA, Harbeck N, et al. Human kallikrein 13 protein in ovarian cancer cytosols: a new favorable prognostic marker. J Clin Oncol 2004; 22(4): 678–685.

    Article  PubMed  CAS  Google Scholar 

  153. Yousef GM, Fracchioli S, Scorilas A, et al. Steroid hormone regulation and prognostic value of the human kallikrein gene 14 in ovarian cancer. Am J Clin Pathol 2003; 119(3): 346–355.

    Article  PubMed  CAS  Google Scholar 

  154. Yousef GM, Scorilas A, Katsaros D, et al. Prognostic value of the human kallikrein gene 15 expression in ovarian cancer. J Clin Oncol 2003; 21(16): 3119–3126.

    Article  PubMed  CAS  Google Scholar 

  155. Xi Z, Kaern J, Davidson B, et al. Kallikrein 4 is associated with paclitaxel resistance in ovarian cancer. Gynecol Oncol 2004; 94(1): 80–85.

    Article  PubMed  CAS  Google Scholar 

  156. Obiezu CV, Scorilas A, Katsaros D, et al. Higher human kallikrein gene 4 (KLK4) expression indicates poor prognosis of ovarian cancer patients. Clin Cancer Res 2001; 7(8): 2380–2386.

    PubMed  CAS  Google Scholar 

  157. Diamandis EP, Borgono CA, Scorilas A, et al. Immunofluorometric quantification of human kallikrein 5 expression in ovarian cancer cytosols and its association with unfavorable patient prognosis. Tumour Biol 2003; 24(6): 299–309.

    Article  PubMed  CAS  Google Scholar 

  158. Kim H, Scorilas A, Katsaros D, et al. Human kallikrein gene 5 (KLK5) expression is an indicator of poor prognosis in ovarian cancer. Br J Cancer 2001; 84(5): 643–650.

    Article  PubMed  CAS  Google Scholar 

  159. Hoffman BR, Katsaros D, Scorilas A, et al. Immunofluorometric quantitation and histochemical localisation of kallikrein 6 protein in ovarian cancer tissue: a new independent unfavourable prognostic biomarker. Br J Cancer 2002; 87(7): 763–771.

    Article  PubMed  CAS  Google Scholar 

  160. Shigemasa K, Tian X, Gu L, et al. Human kallikrein 8 (hK8/TADG-14) expression is associated with an early clinical stage and favorable prognosis in ovarian cancer. OncolRep 2004; 11(6): 1153–1159.

    CAS  Google Scholar 

  161. Magklara A, Scorilas A, Katsaros D, et al. The human KLK8 (neuropsin/ovasin) gene: identification of two novel splice variants and its prognostic value in ovarian cancer. Clin Cancer Res 2001; 7(4): 806–811.

    PubMed  CAS  Google Scholar 

  162. Yousef GM, Kyriakopoulou LG, Scorilas A, et al. Quantitative expression of the human kallikrein gene 9 (KLK9) in ovarian cancer: a new independent and favorable prognostic marker. Cancer Res 2001; 61(21): 7811–7818.

    PubMed  CAS  Google Scholar 

  163. Golub TR, Slonim DK, Tamayo P, et al. Molecular classification of cancer: class discovery and class prediction by gene expression monitoring. Science 1999; 286(5439): 531–537.

    Article  PubMed  CAS  Google Scholar 

  164. Ramaswamy S, Tamayo P, Rifkin R, et al. Multiclass cancer diagnosis using tumor gene expression signatures. Proc Natl Acad Sci USA 2001; 98(26): 15,149-15,154.

    Article  CAS  Google Scholar 

  165. Meinhold-Heerlein I, Bauerschlag D, Hilpert F, et al. Molecular and prognostic distinction between serous ovarian carcinomas of varying grade and malignant potential. Oncogene 2004; 24(6): 1053–1065.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Laboratory of Cellular and Molecular Biology, National Institute on Aging, Baltimore, MD

    Pat J. Morin PhD

Authors
  1. Pat J. Morin PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Sbarro Institute for Cancer Research and Molecular Medicine, Temple University, Philadelphia, PA

    Antonio Giordano MD, PhD  & Alessandro Bovicelli MD, PhD  & 

  2. Departments of Human Pathology and Oncology, University of Siena, Siena, Italy

    Antonio Giordano MD, PhD

  3. Department of Obstetrics and Gynecology, University of Bologna, Bologna, Italy

    Alessandro Bovicelli MD, PhD

  4. Departments of Gynecology-Obstetrics and Pathology, Johns Hopkins University, Baltimore, MD

    Robert J. Kurman MD, PhD

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Humana Press Inc., Totowa, NJ

About this chapter

Cite this chapter

Morin, P.J. (2007). Molecular Markers in Epithelial Ovarian Cancer. In: Giordano, A., Bovicelli, A., Kurman, R.J. (eds) Molecular Pathology of Gynecologic Cancer. Current Clinical Oncology. Humana Press. https://doi.org/10.1007/978-1-59745-346-2_3

Download citation

  • DOI: https://doi.org/10.1007/978-1-59745-346-2_3

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-453-1

  • Online ISBN: 978-1-59745-346-2

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation