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Klinisch-pathologische und molekulare Prognosefaktoren kolorektaler Karzinome

  • Schwerpunkt: Unterer Gastrointestinaltrakt
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Zusammenfassung

In den vergangenen Jahren wurden in zahlreichen Arbeiten verschiedene Aspekte der Progression und Prognose des Dickdarmkarzinoms erforscht. Von grundlegender Bedeutung bleibt die exakte makro- und mikroskopische Untersuchung und Beschreibung. Auf der anderen Seite konnten durch Anwendung neuerer immunhistochemischer und molekularbiologischer Methoden verschiedene Faktoren der molekularen Pathogenese kolorektaler Karzinome beschrieben und hinsichtlich ihrer Bedeutung für den Krankheitsverlauf und die Prognose evaluiert werden. Hierzu gehören insbesondere Unterschiede zwischen den verschiedenen Wegen der Karzinogenese und die Mikrosatelliteninstabilität. Ferner wurde die Erfassung von Mikrometastasen mit Hilfe verschiedener überwiegend molekularer Methoden untersucht. Zahlreiche Onkogene, Tumorsuppressorgene und Zellzyklusregulatoren, Marker für Proliferation und Apoptose, Zelladhäsionsantigene und Angiogenesefaktoren konnten hinsichtlich ihrer prognostischen Bedeutung charakterisiert werden. In der Zukunft werden voraussichtlich auch sog. Responseprädiktoren für eine neoadjuvante (Radio-)Chemotherapie besondere Relevanz gewinnen. Die vorliegende Arbeit soll eine Übersicht über diese Ergebnisse und ihre potenzielle zukünftige klinische Relevanz geben.

Abstract

Various aspects of the progression and prognosis of colorectal carcinoma have been investigated in numerous publications during recent years. An exact macroscopic and microscopic examination is still of basic importance but different factors of the molecular pathogenesis of colorectal carcinoma could be described by immunohistochemistry and molecular biology. Furthermore, they have been evaluated regarding their importance for the course of disease and prognosis and in particular, the different pathways of carcinogenesis and microsatellite instability were included. The detection of micrometastasis was investigated applying mostly molecular genetic methods. Numerous oncogenes, tumor suppressor genes and regulators of the cell cycle, markers of proliferation and apoptosis, cell adhesion antigens and angiogenetic factors were characterized with regard to their prognostic potential. In the future, so-called response predictors will presumably gain a certain relevance in the context of neoadjuvant (radiotherapy) chemotherapy. The present review summarizes these results and discusses the future clinical relevance.

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Literatur

  1. Advanced Colorectal Cancer Meta-Analysis Project (1992) Modulation of fluorouracil by leucovorin in patients with advanced colorectal cancer: evidence in terms of response rate. J Clin Oncol 10:896–903

    PubMed  Google Scholar 

  2. Adell G, Boeryd B, Franlund B et al. (1996) Occurrence and prognostic importance of micrometastases in regional lymph nodes in Dukes' B colorectal carcinoma: an immunohistochemical study. Eur J Surg 162:637–642

    CAS  PubMed  Google Scholar 

  3. Adlard JW, Richman SD, Seymour MT, Quirke P (2002) Prediction of the response of colorectal cancer to systemic therapy. Lancet Oncol 3:75–82

    Article  CAS  PubMed  Google Scholar 

  4. Alexander J, Watanabe T, Wu TT et al. (2001) Histopathological identification of colon cancer with microsatellite instability. Am J Pathol 158:527–535

    CAS  PubMed  Google Scholar 

  5. Andreyev HJ, Norman AR, Cunningham D et al. (1998) Kirsten ras mutations in patients with colorectal cancer: the multicenter "RASCAL" study. J Natl Cancer Inst 90:675–684

    Article  CAS  PubMed  Google Scholar 

  6. Aschele C, Lonardi S, Monfardini S (2002) Thymidylate synthase expression as a predictor of clinical response to fluoropyrimidine-based chemotherapy in advanced colorectal cancer. Cancer Treat Rev 28:27–47

    Article  CAS  PubMed  Google Scholar 

  7. Augenlicht LH, Wadler S, Corner G et al. (1997) Low-level c-myc amplification in human colonic carcinoma cell lines and tumors: a frequent, p53-independent mutation associated with improved outcome in a randomized multi-institutional trial. Cancer Res 57:1769–1775

    CAS  PubMed  Google Scholar 

  8. Baldus SE, Hanisch FG (2000) Biochemistry and pathological importance of mucin-associated antigens in gastrointestinal neoplasia. Adv Cancer Res 79:201–248

    CAS  PubMed  Google Scholar 

  9. Baldus SE, Hanisch FG, Kotlarek GM et al. (1998) Coexpression of MUC1 mucin peptide core and the Thomsen-Friedenreich antigen in colorectal neoplasms. Cancer 82:1019–1027

    Article  CAS  PubMed  Google Scholar 

  10. Baldus SE, Monig SP, Hanisch FG et al. (2002) Comparative evaluation of the prognostic value of MUC1, MUC2, sialyl-Lewis(a) and sialyl-Lewis(x) antigens in colorectal adenocarcinoma. Histopathology 40:440–449

    Article  CAS  PubMed  Google Scholar 

  11. Baldus SE, Zirbes TK, Hanisch FG et al. (2000) Thomsen-Friedenreich antigen presents as a prognostic factor in colorectal carcinoma: a clinicopathologic study of 264 patients. Cancer 88:1536–1543

    Article  CAS  PubMed  Google Scholar 

  12. Baretton GB, Diebold J, Christoforis G et al. (1996) Apoptosis and immunohistochemical bcl-2 expression in colorectal adenomas and carcinomas. Aspects of carcinogenesis and prognostic significance. Cancer 77:255–264

    Article  CAS  PubMed  Google Scholar 

  13. Belluco C, Esposito G, Bertorelle R et al. (1999) Absence of the cell cycle inhibitor p27Kip1 protein predicts poor outcome in patients with stage I-III colorectal cancer. Ann Surg Oncol 6:19–25

    CAS  PubMed  Google Scholar 

  14. Biemer-Huttmann AE, Walsh MD, McGuckin MA et al. (2000) Mucin core protein expression in colorectal cancers with high levels of microsatellite instability indicates a novel pathway of morphogenesis. Clin Cancer Res 6:1909–1916

    CAS  PubMed  Google Scholar 

  15. Bosari S, Moneghini L, Graziani D et al. (1995) bcl-2 oncoprotein in colorectal hyperplastic polyps, adenomas, and adenocarcinomas. Hum Pathol 26:534–540

    CAS  PubMed  Google Scholar 

  16. Bosman FT (1999) Molecular pathology of colorectal cancer. Cytogenet Cell Genet 86:112–117

    Article  CAS  PubMed  Google Scholar 

  17. Brabletz T, Jung A, Kirchner T (2002) beta-Catenin and the morphogenesis of colorectal cancer. Virchows Arch 441:1–11

    CAS  PubMed  Google Scholar 

  18. Broll R, Schauer V, Schimmelpenning H et al. (1997) Prognostic relevance of occult tumor cells in lymph nodes of colorectal carcinomas: an immunohistochemical study. Dis Colon Rectum 40:1465–1471

    Google Scholar 

  19. Bubb VJ, Curtis LJ, Cunningham C et al. (1996) Microsatellite instability and the role of hMSH2 in sporadic colorectal cancer. Oncogene 12:2641–2649

    CAS  PubMed  Google Scholar 

  20. Buglioni S, D'Agnano I, Cosimelli M et al. (1999) Evaluation of multiple bio-pathological factors in colorectal adenocarcinomas: independent prognostic role of p53 and bcl-2. Int J Cancer 84:545–552

    Article  CAS  PubMed  Google Scholar 

  21. Calaluce R, Miedema BW, Yesus YW (1998) Micrometastasis in colorectal carcinoma: a review. J Surg Oncol 67:194–202

    Article  CAS  PubMed  Google Scholar 

  22. Calin GA, Gafa R, Tibiletti MG et al. (2000) Genetic progression in microsatellite instability high (MSI-H) colon cancers correlates with clinico-pathological parameters: A study of the TGRbetaRII, BAX, hMSH3, hMSH6, IGFIIR and BLM genes. Int J Cancer 89:230–235

    CAS  PubMed  Google Scholar 

  23. Caplin S, Cerottini JP, Bosman FT et al. (1998) For patients with Dukes' B (TNM Stage II) colorectal carcinoma, examination of six or fewer lymph nodes is related to poor prognosis. Cancer 83:666–672

    Article  CAS  PubMed  Google Scholar 

  24. Chung GG, Provost E, Kielhorn EP et al. (2001) Tissue microarray analysis of beta-catenin in colorectal cancer shows nuclear phospho-beta-catenin is associated with a better prognosis. Clin Cancer Res 7:4013–4020

    CAS  PubMed  Google Scholar 

  25. Chung YF, Eu KW, Machin D et al. (1998) Young age is not a poor prognostic marker in colorectal cancer. Br J Surg 85:1255–1259

    Article  CAS  PubMed  Google Scholar 

  26. Coca S, Perez-Piqueras J, Martinez D et al. (1997) The prognostic significance of intratumoral natural killer cells in patients with colorectal carcinoma. Cancer 79:2320–2328

    Article  CAS  PubMed  Google Scholar 

  27. Compton CC (1999) Pathology report in colon cancer: what is prognostically important? Dig Dis 17:67–79

    CAS  PubMed  Google Scholar 

  28. Consorti F, Lorenzotti A, Midiri G, Di Paola M (2000) Prognostic significance of mucinous carcinoma of colon and rectum: a prospective case-control study. J Surg Oncol 73:70–74

    Article  CAS  PubMed  Google Scholar 

  29. Corfield AP, Carroll D, Myerscough N, Probert CS (2001) Mucins in the gastrointestinal tract in health and disease. Front Biosci 6:D1321–1357

    CAS  PubMed  Google Scholar 

  30. Duffy MJ, Maguire TM, McDermott EW, O'Higgins N (1999) Urokinase plasminogen activator: a prognostic marker in multiple types of cancer. J Surg Oncol 71:130–135

    Article  CAS  PubMed  Google Scholar 

  31. Edmonston TB, Cuesta KH, Burkholder S et al. (2000) Colorectal carcinomas with high microsatellite instability: defining a distinct immunologic and molecular entity with respect to prognostic markers. Hum Pathol 31:1506–1514

    CAS  PubMed  Google Scholar 

  32. Esteller M, Tortola S, Toyota M et al. (2000) Hypermethylation-associated inactivation of p14(ARF) is independent of p16(INK4a) methylation and p53 mutational status. Cancer Res 60:129–133

    CAS  PubMed  Google Scholar 

  33. Evertsson S, Bartik Z, Zhang H et al. (1999) Apoptosis in relation to proliferating cell nuclear antigen and Dukes' stage in colorectal adenocarcinoma. Int J Oncol 15:53–58

    CAS  PubMed  Google Scholar 

  34. Fearnhead NS, Britton MP, Bodmer WF (2001) The ABC of APC. Hum Mol Genet 10:721–733

    Article  CAS  PubMed  Google Scholar 

  35. Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767

    PubMed  Google Scholar 

  36. Fernandez-Acenero MJ, Galindo-Gallego M, Sanz J, Aljama A (2000) Prognostic influence of tumor-associated eosinophilic infiltrate in colorectal carcinoma. Cancer 88:1544–1548

    Article  CAS  PubMed  Google Scholar 

  37. Fodde R (2002) The APC gene in colorectal cancer. Eur J Cancer 38:867–871

    Article  CAS  PubMed  Google Scholar 

  38. Fujita S, Moriya Y, Sugihara K et al. (1996) Prognosis of hereditary nonpolyposis colorectal cancer (HNPCC) and the role of Japanese criteria for HNPCC. Jpn J Clin Oncol 26:351–355

    CAS  PubMed  Google Scholar 

  39. Gafa R, Maestri I, Matteuzzi M et al. (2000) Sporadic colorectal adenocarcinomas with high-frequency microsatellite instability. Cancer 89:2025–2037

    Article  CAS  PubMed  Google Scholar 

  40. Giatromanolaki A, Sivridis E, Stathopoulos GP et al. (2001) Bax protein expression in colorectal cancer: association with p53, bcl-2 and patterns of relapse. Anticancer Res 21:253–259

    CAS  PubMed  Google Scholar 

  41. Giatromanolaki A, Stathopoulos GP, Tsiobanou E et al. (1999) Combined role of tumor angiogenesis, bcl-2, and p53 expression in the prognosis of patients with colorectal carcinoma. Cancer 86:1421–1430

    Article  CAS  PubMed  Google Scholar 

  42. Grabowski P, Mann B, Mansmann U et al. (2000) Expression of SIALYL-Le(x) antigen defined by MAb AM-3 is an independent prognostic marker in colorectal carcinoma patients. Int J Cancer 88:281-286

    Article  CAS  PubMed  Google Scholar 

  43. Grady WM, Rajput A, Myeroff L et al. (1998) Mutation of the type II transforming growth factor-beta receptor is coincident with the transformation of human colon adenomas to malignant carcinomas. Cancer Res 58:3101-3104

    CAS  PubMed  Google Scholar 

  44. Graf W, Glimelius B, Pahlman L, Bergstrom R (1991) Determinants of prognosis in advanced colorectal cancer. Eur J Cancer 27:1119–1123

    CAS  PubMed  Google Scholar 

  45. Green JB, Timmcke AE, Mitchell WT et al. (1993) Mucinous carcinoma--just another colon cancer? Dis Colon Rectum 36:49–54

    Google Scholar 

  46. Greenson JK, Isenhart CE, Rice R et al. (1994) Identification of occult micrometastases in pericolic lymph nodes of Duke's B colorectal cancer patients using monoclonal antibodies against cytokeratin and CC49. Correlation with long-term survival. Cancer 73:563–569

    CAS  PubMed  Google Scholar 

  47. Grizzle WE, Manne U, Jhala NC, Weiss HL (2001) Molecular characterization of colorectal neoplasia in translational research. Arch Pathol Lab Med 125:91–98

    CAS  PubMed  Google Scholar 

  48. Grizzle WE, Manne U, Weiss HL et al. (2002) Molecular staging of colorectal cancer in African-American and Caucasian patients using phenotypic expression of p53, Bcl-2, MUC-1 AND p27(kip-1). Int J Cancer 97:403–409

    Article  CAS  PubMed  Google Scholar 

  49. Gryfe R, Kim H, Hsieh ET et al. (2000) Tumor microsatellite instability and clinical outcome in young patients with colorectal cancer. N Engl J Med 342:69–77

    CAS  PubMed  Google Scholar 

  50. Gunther K, Brabletz T, Kraus C et al. (1998) Predictive value of nuclear beta-catenin expression for the occurrence of distant metastases in rectal cancer. Dis Colon Rectum 41:1256–1261

    Google Scholar 

  51. Gunthert U, Stauder R, Mayer B et al. (1995) Are CD44 variant isoforms involved in human tumour progression? Cancer Surv 24:19–42

    CAS  PubMed  Google Scholar 

  52. Haier J, Nasralla M, Nicolson GL (2000) Cell surface molecules and their prognostic values in assessing colorectal carcinomas. Ann Surg 231:11–24

    Article  CAS  PubMed  Google Scholar 

  53. Halling KC, French AJ, McDonnell SK et al. (1999) Microsatellite instability and 8p allelic imbalance in stage B2 and C colorectal cancers. J Natl Cancer Inst 91:1295–1303

    Article  CAS  PubMed  Google Scholar 

  54. Halvorsen TB, Seim E (1988) Degree of differentiation in colorectal adenocarcinomas: a multivariate analysis of the influence on survival. J Clin Pathol 41:532–537

    CAS  PubMed  Google Scholar 

  55. Handa K, Yamakawa M, Takeda H et al. (1999) Expression of cell cycle markers in colorectal carcinoma: superiority of cyclin A as an indicator of poor prognosis. Int J Cancer 84:225–233

    Article  CAS  PubMed  Google Scholar 

  56. Harrison JC, Dean PJ, el-Zeky F, Vander Zwaag R (1994) From Dukes through Jass: pathological prognostic indicators in rectal cancer. Hum Pathol 25:498–505

    CAS  PubMed  Google Scholar 

  57. Hayashi N, Ito I, Yanagisawa A et al. (1995) Genetic diagnosis of lymph-node metastasis in colorectal cancer. Lancet 345:1257–1259

    CAS  PubMed  Google Scholar 

  58. He TC, Sparks AB, Rago C et al. (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512

    Article  CAS  PubMed  Google Scholar 

  59. Hermanek P (1986) Gastrointestinal carcinoma—are there age-related differences in tumor behavior? Hepatogastroenterology 33:180–183

    CAS  PubMed  Google Scholar 

  60. Hermanek P, Mansmann U, Staimmer DS, Riedl S (2000) The German experience: the surgeon as a prognostic factor in colon and rectal cancer surgery. Surg Oncol Clin North Am 9:33–49, vi

    CAS  Google Scholar 

  61. Hermanek P, Wittekind C (1994) Residual tumor (R) classification and prognosis. Semin Surg Oncol 10:12–20

    CAS  PubMed  Google Scholar 

  62. Hiraga Y, Tanaka S, Haruma K et al. (1998) Immunoreactive MUC1 expression at the deepest invasive portion correlates with prognosis of colorectal cancer. Oncology 55:307–319

    Google Scholar 

  63. Hobday TJ, Erlichman C (2001) Colorectal cancer. In: Gospodarowicz MK, Henson DE, Hutter RVP et al. (eds) Prognostic factors in cancer. Wiley-Liss, New York, pp 267–280

  64. Holland TA, Elder J, McCloud JM et al. (2001) Subcellular localisation of cyclin D1 protein in colorectal tumours is associated with p21(WAF1/CIP1) expression and correlates with patient survival. Int J Cancer 95:302–306

    Article  CAS  PubMed  Google Scholar 

  65. Houlston RS (2001) What we could do now: molecular pathology of colorectal cancer. Mol Pathol 54:206–214

    Article  CAS  PubMed  Google Scholar 

  66. Houlston RS, Tomlinson IP (2001) Polymorphisms and colorectal tumor risk. Gastroenterology 121:282–301

    CAS  PubMed  Google Scholar 

  67. Ilyas M, Tomlinson IP, Hanby A et al. (1997) Allele loss, replication errors and loss of expression of E-cadherin in colorectal cancers. Gut 40:654–659

    CAS  PubMed  Google Scholar 

  68. Ilyas M, Tomlinson IP, Novelli MR et al. (1996) Clinico-pathological features and p53 expression in left-sided sporadic colorectal cancers with and without microsatellite instability. J Pathol 179:370–375

    Article  CAS  PubMed  Google Scholar 

  69. Iqbal S, Lenz HJ (2001) Determinants of prognosis and response to therapy in colorectal cancer. Curr Oncol Rep 3:102–108

    CAS  PubMed  Google Scholar 

  70. Itzkowitz SH, Bloom EJ, Kokal WA et al. (1990) Sialosyl-Tn. A novel mucin antigen associated with prognosis in colorectal cancer patients. Cancer 66:1960–1966

    CAS  PubMed  Google Scholar 

  71. Izbicki JR, Hosch SB, Knoefel WT et al. (1995) Extended resections are beneficial for patients with locally advanced colorectal cancer. Dis Colon Rectum 38:1251–1256

    Google Scholar 

  72. Jansson A, Sun XF (1997) Ki-67 expression in relation to clinicopathological variables and prognosis in colorectal adenocarcinomas. Apmis 105:730–734

    CAS  PubMed  Google Scholar 

  73. Jass JR, Do KA, Simms LA et al. (1998) Morphology of sporadic colorectal cancer with DNA replication errors. Gut 42:673–679

    CAS  PubMed  Google Scholar 

  74. Jass JR, Whitehall VL, Young J, Leggett BA (2002) Emerging concepts in colorectal neoplasia. Gastroenterology 123:862–876

    Article  CAS  PubMed  Google Scholar 

  75. Jeffers MD, O'Dowd GM, Mulcahy H et al. (1994) The prognostic significance of immunohistochemically detected lymph node micrometastases in colorectal carcinoma. J Pathol 172:183–187

    CAS  PubMed  Google Scholar 

  76. Jernvall P, Makinen MJ, Karttunen TJ et al. (1999) Microsatellite instability: impact on cancer progression in proximal and distal colorectal cancers. Eur J Cancer 35:197–201

    Article  CAS  PubMed  Google Scholar 

  77. Kaklamanis L, Savage A, Whitehouse R et al. (1998) Bcl-2 protein expression: association with p53 and prognosis in colorectal cancer. Br J Cancer 77:1864–1869

    CAS  PubMed  Google Scholar 

  78. Kapiteijn E, Liefers GJ, Los LC et al. (2001) Mechanisms of oncogenesis in colon versus rectal cancer. J Pathol 195:171–178

    Article  CAS  PubMed  Google Scholar 

  79. Kawamoto K, Onodera H, Kondo S et al. (1998) Expression of insulin-like growth factor-2 can predict the prognosis of human colorectal cancer patients: correlation with tumor progression, proliferative activity and survival. Oncology 55:242–248

    Google Scholar 

  80. Khandwala HM, McCutcheon IE, Flyvbjerg A, Friend KE (2000) The effects of insulin-like growth factors on tumorigenesis and neoplastic growth. Endocr Rev 21:215–244

    CAS  PubMed  Google Scholar 

  81. Kimura T, Tanaka S, Haruma K et al. (2000) Clinical significance of MUC1 and E-cadherin expression, cellular proliferation, and angiogenesis at the deepest invasive portion of colorectal cancer. Int J Oncol 16:55–64

    CAS  PubMed  Google Scholar 

  82. Kubota Y, Petras RE, Easley KA et al. (1992) Ki-67-determined growth fraction versus standard staging and grading parameters in colorectal carcinoma. A multivariate analysis. Cancer 70:2602–2609

    CAS  PubMed  Google Scholar 

  83. Kyzer S, Gordon PH (1997) Determination of proliferative activity in colorectal carcinoma using monoclonal antibody Ki67. Dis Colon Rectum 40:322–325

    Google Scholar 

  84. Lanza G, Matteuzzi M, Gafa R et al. (1998) Chromosome 18q allelic loss and prognosis in stage II and III colon cancer. Int J Cancer 79:390–395

    Article  CAS  PubMed  Google Scholar 

  85. Laurent-Puig P, Blons H, Cugnenc PH (1999) Sequence of molecular genetic events in colorectal tumorigenesis. Eur J Cancer Prev 8 [Suppl 1]:S39–47

    Google Scholar 

  86. Leahy DT, Mulcahy HE, O'Donoghue DP, Parfrey NA (1999) bcl-2 protein expression is associated with better prognosis in colorectal cancer. Histopathology 35:360–367

    Article  CAS  PubMed  Google Scholar 

  87. Lee JC, Chow NH, Wang ST, Huang SM (2000) Prognostic value of vascular endothelial growth factor expression in colorectal cancer patients. Eur J Cancer 36:748–753

    Article  CAS  PubMed  Google Scholar 

  88. Lee PY, Fletcher WS, Sullivan ES, Vetto JT (1994) Colorectal cancer in young patients: characteristics and outcome. Am Surg 60:607–612

    CAS  PubMed  Google Scholar 

  89. Li JQ, Miki H, Ohmori M et al. (2001) Expression of cyclin E and cyclin-dependent kinase 2 correlates with metastasis and prognosis in colorectal carcinoma. Hum Pathol 32:945–953

    Article  CAS  PubMed  Google Scholar 

  90. Liefers GJ, Cleton-Jansen AM, van de Velde CJ et al. (1998) Micrometastases and survival in stage II colorectal cancer. N Engl J Med 339:223–228

    CAS  PubMed  Google Scholar 

  91. Loda M, Cukor B, Tam SW et al. (1997) Increased proteasome-dependent degradation of the cyclin-dependent kinase inhibitor p27 in aggressive colorectal carcinomas. Nat Med 3:231–234

    CAS  PubMed  Google Scholar 

  92. Maeda K, Chung YS, Kang SM et al. (1997) Overexpression of cyclin D1 and p53 associated with disease recurrence in colorectal adenocarcinoma. Int J Cancer 74:310–315

    Article  CAS  PubMed  Google Scholar 

  93. Manne U, Myers RB, Moron C et al. (1997) Prognostic significance of Bcl-2 expression and p53 nuclear accumulation in colorectal adenocarcinoma. Int J Cancer 74:346–358

    Article  CAS  PubMed  Google Scholar 

  94. McArdle CS, Hole D (1991) Impact of variability among surgeons on postoperative morbidity and mortality and ultimate survival. Bmj 302:1501–1505

    CAS  PubMed  Google Scholar 

  95. McKay JA, Douglas JJ, Ross VG et al. (2002) Analysis of key cell-cycle checkpoint proteins in colorectal tumours. J Pathol 196:386–393

    Article  CAS  PubMed  Google Scholar 

  96. McLeod HL, Murray GI (1999) Tumour markers of prognosis in colorectal cancer. Br J Cancer 79:191–203

    CAS  PubMed  Google Scholar 

  97. Messerini L, Palomba A, Zampi G (1995) Primary signet-ring cell carcinoma of the colon and rectum. Dis Colon Rectum 38:1189–1192

    Google Scholar 

  98. Michael-Robinson JM, Reid LE, Purdie DM et al. (2001) Proliferation, apoptosis, and survival in high-level microsatellite instability sporadic colorectal cancer. Clin Cancer Res 7:2347–2356

    CAS  PubMed  Google Scholar 

  99. Moertel CG, Fleming TR, Macdonald JS et al. (1995) Fluorouracil plus levamisole as effective adjuvant therapy after resection of stage III colon carcinoma: a final report. Ann Intern Med 122:321–326

    CAS  PubMed  Google Scholar 

  100. Mohri Y (1997) Prognostic significance of E-cadherin expression in human colorectal cancer tissue. Surg Today 27:606–612

    CAS  PubMed  Google Scholar 

  101. Mulder JW, Kruyt PM, Sewnath M et al. (1994) Colorectal cancer prognosis and expression of exon-v6-containing CD44 proteins. Lancet 344:1470–1472

    CAS  PubMed  Google Scholar 

  102. Muller A, Fishel R (2002) Mismatch repair and the hereditary non-polyposis colorectal cancer syndrome (HNPCC). Cancer Invest 20:102–109

    Article  PubMed  Google Scholar 

  103. Murray GI, Duncan ME, O'Neil P et al. (1996) Matrix metalloproteinase-1 is associated with poor prognosis in colorectal cancer. Nat Med 2:461–462

    CAS  PubMed  Google Scholar 

  104. Nakamori S, Kameyama M, Imaoka S et al. (1997) Involvement of carbohydrate antigen sialyl Lewis(x) in colorectal cancer metastasis. Dis Colon Rectum 40:420–431

    Google Scholar 

  105. Nakayama T, Watanabe M, Katsumata T et al. (1995) Expression of sialyl Lewis(a) as a new prognostic factor for patients with advanced colorectal carcinoma. Cancer 75:2051–2056

    CAS  PubMed  Google Scholar 

  106. Nihei Z, Ichikawa W, Kojima K et al. (1996) The positive relationship between the expression of CD44 variant 6 and prognosis in colorectal cancer. Surg Today 26:760–761

    CAS  PubMed  Google Scholar 

  107. Nissan A, Guillem JG, Paty PB et al. (1999) Signet-ring cell carcinoma of the colon and rectum: a matched control study. Dis Colon Rectum 42:1176–1180

    Google Scholar 

  108. Nozoe T, Anai H, Nasu S, Sugimachi K (2000) Clinicopathological characteristics of mucinous carcinoma of the colon and rectum. J Surg Oncol 75:103–107

    Article  CAS  PubMed  Google Scholar 

  109. Oberg A, Stenling R, Tavelin B, Lindmark G (1998) Are lymph node micrometastases of any clinical significance in Dukes stages A and B colorectal cancer? Dis Colon Rectum 41:1244–1249

    Google Scholar 

  110. O'Connell MJ, Martenson JA, Wieand HS et al. (1994) Improving adjuvant therapy for rectal cancer by combining protracted-infusion fluorouracil with radiation therapy after curative surgery. N Engl J Med 331:502–507

    Article  CAS  PubMed  Google Scholar 

  111. Ofner D, Grothaus A, Riedmann B et al. (1996) MIB1 in colorectal carcinomas: its evaluation by three different methods reveals lack of prognostic significance. Anal Cell Pathol 12:61–70

    CAS  PubMed  Google Scholar 

  112. Ougolkov AV, Yamashita K, Mai M, Minamoto T (2002) Oncogenic beta-catenin and MMP-7 (matrilysin) cosegregate in late-stage clinical colon cancer. Gastroenterology 122:60–71

    Google Scholar 

  113. Palmqvist R, Stenling R, Oberg A, Landberg G (1998) Expression of cyclin D1 and retinoblastoma protein in colorectal cancer. Eur J Cancer 34:1575–1581

    Article  CAS  PubMed  Google Scholar 

  114. Palmqvist R, Stenling R, Oberg A, Landberg G (1999) Prognostic significance of p27(Kip1) expression in colorectal cancer: a clinico-pathological characterization. J Pathol 188:18–23

    Article  CAS  PubMed  Google Scholar 

  115. Papamichael D (2001) Prognostic role of angiogenesis in colorectal cancer. Anticancer Res 21:4349–4353

    CAS  PubMed  Google Scholar 

  116. Parramore JB, Wei JP, Yeh KA (1998) Colorectal cancer in patients under forty: presentation and outcome. Am Surg 64:563–567; discussion 567–568

    CAS  PubMed  Google Scholar 

  117. Pasche B, Mulcahy M, Benson AB 3rd (2002) Molecular markers in prognosis of colorectal cancer and prediction of response to treatment. Best Pract Res Clin Gastroenterol 16:331–345

    Article  PubMed  Google Scholar 

  118. Perrin J, Gouvernet J, Parriaux D et al. (2001) MSH2 and MLH1 immunodetection and the prognosis of colon cancer. Int J Oncol 19:891–895

    CAS  PubMed  Google Scholar 

  119. Perucho M (1996) Cancer of the microsatellite mutator phenotype. Biol Chem 377:675–684

    CAS  PubMed  Google Scholar 

  120. Poller DN, Baxter KJ, Shepherd NA (1997) p53 and Rb1 protein expression: are they prognostically useful in colorectal cancer? Br J Cancer 75:87–93

    CAS  PubMed  Google Scholar 

  121. Ponz de Leon M, Sant M, Micheli A et al. (1992) Clinical and pathologic prognostic indicators in colorectal cancer. A population-based study. Cancer 69:626–635

    PubMed  Google Scholar 

  122. Prandi M, Lionetto R, Bini A et al. (2002) Prognostic evaluation of stage B colon cancer patients is improved by an adequate lymphadenectomy: results of a secondary analysis of a large scale adjuvant trial. Ann Surg 235:458–463

    Article  PubMed  Google Scholar 

  123. Pullarkat ST, Stoehlmacher J, Ghaderi V et al. (2001) Thymidylate synthase gene polymorphism determines response and toxicity of 5-FU chemotherapy. Pharmacogenomics J 1:65–70

    CAS  PubMed  Google Scholar 

  124. Roncucci L, Fante R, Losi L et al. (1996) Survival for colon and rectal cancer in a population-based cancer registry. Eur J Cancer 32A:295–302

    Article  CAS  PubMed  Google Scholar 

  125. Ropponen KM, Kellokoski JK, Lipponen PK et al. (1999) p21/WAF1 expression in human colorectal carcinoma: association with p53, transcription factor AP-2 and prognosis. Br J Cancer 81:133–140

    Article  CAS  PubMed  Google Scholar 

  126. Rosenberg R, Hoos A, Mueller J, Nekarda H (2000) Impact of cytokeratin-20 and carcinoembryonic antigen mRNA detection by RT-PCR in regional lymph nodes of patients with colorectal cancer. Br J Cancer 83:1323–1329

    Article  CAS  PubMed  Google Scholar 

  127. Ross JS, McKenna BJ (2001) The HER-2/neu oncogene in tumors of the gastrointestinal tract. Cancer Invest 19:554–568

    Article  CAS  PubMed  Google Scholar 

  128. Rüschoff J, Dietmaier W, Bocker T et al. (1998) Molekulare Krebsdispositionsdiagnostik am Beispiel des kolorektalen Karzinoms. Welchen Beitrag kann die Pathologie leisten? Pathologe 19:269–278

    Article  CAS  PubMed  Google Scholar 

  129. Rüschoff J, Dietmaier W, Luttges J et al. (1997) Poorly differentiated colonic adenocarcinoma, medullary type: clinical, phenotypic, and molecular characteristics. Am J Pathol 150:1815–1825

    CAS  PubMed  Google Scholar 

  130. Sahin AA, Ro JY, Brown RW et al. (1994) Assessment of Ki-67-derived tumor proliferative activity in colorectal adenocarcinomas. Mod Pathol 7:17–22

    CAS  PubMed  Google Scholar 

  131. Salahshor S, Kressner U, Fischer H et al. (1999) Microsatellite instability in sporadic colorectal cancer is not an independent prognostic factor. Br J Cancer 81:190–193

    Article  CAS  PubMed  Google Scholar 

  132. Samowitz WS, Curtin K, Ma KN et al. (2002) Prognostic significance of p53 mutations in colon cancer at the population level. Int J Cancer 99:597–602

    Article  CAS  PubMed  Google Scholar 

  133. Sankila R, Aaltonen LA, Jarvinen HJ, Mecklin JP (1996) Better survival rates in patients with MLH1-associated hereditary colorectal cancer. Gastroenterology 110:682–687

    CAS  PubMed  Google Scholar 

  134. Schelwies K, Sturm I, Grabowski P et al. (2002) Analysis of p53/BAX in primary colorectal carcinoma: low BAX protein expression is a negative prognostic factor in UICC stage III tumors. Int J Cancer 99:589–596

    Article  CAS  PubMed  Google Scholar 

  135. Schneider HJ, Sampson SA, Cunningham D et al. (1997) Bcl-2 expression and response to chemotherapy in colorectal adenocarcinomas. Br J Cancer 75:427–431

    CAS  PubMed  Google Scholar 

  136. Shibata D, Reale MA, Lavin P et al. (1996) The DCC protein and prognosis in colorectal cancer. N Engl J Med 335:1727–1732

    PubMed  Google Scholar 

  137. Shirota Y, Stoehlmacher J, Brabender J et al. (2001) ERCC1 and thymidylate synthase mRNA levels predict survival for colorectal cancer patients receiving combination oxaliplatin and fluorouracil chemotherapy. J Clin Oncol 19:4298–4304

    CAS  PubMed  Google Scholar 

  138. Sinicrope FA, Hart J, Hsu HA et al. (1999) Apoptotic and mitotic indices predict survival rates in lymph node-negative colon carcinomas. Clin Cancer Res 5:1793–1804

    CAS  PubMed  Google Scholar 

  139. Stoehlmacher J, Park DJ, Zhang W et al. (2002) Association between glutathione S-transferase P1, T1, and M1 genetic polymorphism and survival of patients with metastatic colorectal cancer. J Natl Cancer Inst 94:936–942

    Article  CAS  PubMed  Google Scholar 

  140. Streit M, Schmidt R, Hilgenfeld RU et al. (1996) Adhesion receptors in malignant transformation and dissemination of gastrointestinal tumors. Recent Results Cancer Res 142:19–50

    CAS  PubMed  Google Scholar 

  141. Sugamura K, Makino M, Kaibara N (1998) Apoptosis as a prognostic factor in colorectal carcinoma. Surg Today 28:145–150

    Article  CAS  PubMed  Google Scholar 

  142. Sugao Y, Yao T, Kubo C, Tsuneyoshi M (1997) Improved prognosis of solid-type poorly differentiated colorectal adenocarcinoma: a clinicopathological and immunohistochemical study. Histopathology 31:123–133

    CAS  PubMed  Google Scholar 

  143. Sun XF, Carstensen JM, Stal O et al. (1996) Interrelations of clinicopathologic variables and their prognostic value in colorectal adenocarcinoma. Apmis 104:35–38

    CAS  PubMed  Google Scholar 

  144. Takebayashi Y, Akiyama S, Akiba S et al. (1996) Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 88:1110–1117

    CAS  PubMed  Google Scholar 

  145. Tenjo T, Toyoda M, Okuda J et al. (2000) Prognostic significance of p27(kip1) protein expression and spontaneous apoptosis in patients with colorectal adenocarcinomas. Oncology 58:45–51

    Google Scholar 

  146. Theodoropoulos GE, Panoussopoulos D, Lazaris AC, Golematis BC (1997) Evaluation of cathepsin D immunostaining in colorectal adenocarcinoma. J Surg Oncol 65:242–248

    Article  CAS  PubMed  Google Scholar 

  147. Tsavellas G, Patel H, Allen-Mersh TG (2001) Detection and clinical significance of occult tumour cells in colorectal cancer. Br J Surg 88:1307–1320

    Article  CAS  PubMed  Google Scholar 

  148. Tschmelitsch J, Klimstra DS, Cohen AM (2000) Lymph node micrometastases do not predict relapse in stage II colon cancer. Ann Surg Oncol 7:601–608

    CAS  PubMed  Google Scholar 

  149. Umpleby HC, Ranson DL, Williamson RC (1985) Peculiarities of mucinous colorectal carcinoma. Br J Surg 72:715–718

    CAS  PubMed  Google Scholar 

  150. van Triest B, Pinedo HM, Blaauwgeers JL et al. (2000) Prognostic role of thymidylate synthase, thymidine phosphorylase/platelet-derived endothelial cell growth factor, and proliferation markers in colorectal cancer. Clin Cancer Res 6:1063–1072

    PubMed  Google Scholar 

  151. Viale G, Pellegrini C, Mazzarol G et al. (1999) p21WAF1/CIP1 expression in colorectal carcinoma correlates with advanced disease stage and p53 mutations. J Pathol 187:302–307

    Article  CAS  PubMed  Google Scholar 

  152. Vierbuchen MJ, Fruechtnicht W, Brackrock S et al. (1995) Quantitative lectin-histochemical and immunohistochemical studies on the occurrence of alpha(2,3)- and alpha(2,6)-linked sialic acid residues in colorectal carcinomas. Relation to clinicopathologic features. Cancer 76:727–735

    CAS  PubMed  Google Scholar 

  153. Wielenga VJ, van der Voort R, Taher TE et al. (2000) Expression of c-Met and heparan-sulfate proteoglycan forms of CD44 in colorectal cancer. Am J Pathol 157:1563–1573

    CAS  PubMed  Google Scholar 

  154. Wolmark N, Rockette H, Fisher B et al. (1993) The benefit of leucovorin-modulated fluorouracil as postoperative adjuvant therapy for primary colon cancer: results from National Surgical Adjuvant Breast and Bowel Project protocol C-03. J Clin Oncol 11:1879–1887

    CAS  PubMed  Google Scholar 

  155. Yamaguchi A, Urano T, Goi T et al. (1996) Expression of a CD44 variant containing exons 8 to 10 is a useful independent factor for the prediction of prognosis in colorectal cancer patients. J Clin Oncol 14:1122–1127

    CAS  PubMed  Google Scholar 

  156. Yang JL, Seetoo D, Wang Y et al. (2000) Urokinase-type plasminogen activator and its receptor in colorectal cancer: independent prognostic factors of metastasis and cancer-specific survival and potential therapeutic targets. Int J Cancer 89:431–439

    Article  CAS  PubMed  Google Scholar 

  157. Yao J, Eu KW, Seow-Choen F, Cheah PY (2000) Down-regulation of p27 is a significant predictor of poor overall survival and may facilitate metastasis in colorectal carcinomas. Int J Cancer 89:213–216

    Article  CAS  PubMed  Google Scholar 

  158. Zeng ZS, Huang Y, Cohen AM, Guillem JG (1996) Prediction of colorectal cancer relapse and survival via tissue RNA levels of matrix metalloproteinase-9. J Clin Oncol 14:3133–3140

    CAS  PubMed  Google Scholar 

  159. Zhang H, Sun XF (2001) Loss of p27 expression predicts poor prognosis in patients with Dukes' B stage or proximal colorectal cancer. Int J Oncol 19:49–52

    CAS  PubMed  Google Scholar 

  160. Zirbes TK, Baldus SE, Moenig SP et al. (2000) Prognostic impact of p21/waf1/cip1 in colorectal cancer. Int J Cancer 89:14–18

    Article  CAS  PubMed  Google Scholar 

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  1. Institut für Pathologie, Universität zu Köln

    S. E. Baldus

  2. Institut für Pathologie, Universität zu Köln, Joseph-Stelzmann-Straße 9, 50924 , Köln

    S. E. Baldus

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Baldus, S.E. Klinisch-pathologische und molekulare Prognosefaktoren kolorektaler Karzinome. Pathologe 24, 49–60 (2003). https://doi.org/10.1007/s00292-002-0592-7

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