Skip to main content
SpringerLink
Log in

Prognostic Significance of Molecular Biological and Immunohistological Parameters in Gastrointestinal Carcinomas

  • Conference paper
New Perspectives in Molecular and Clinical Management of Gastrointestinal Tumors

Part of the book series: Recent Results in Cancer Research ((RECENTCANCER,volume 142))

Abstract

Histological type, malignancy grade, and tumor stage are among the most important parameters predicting outcome in cancer patients Making use of immunocytochemistry as well as polymerase chain reaction-based techniques the demonstration of micrometastatic tumor spread, for example, into bone marrow, lymph nodes, and peritoneal cavity, is a new staging parameter of prognostic significance. In contrast, the prognostic value of different proliferation markers such as Ki67 (Mib 1), PCNA, and AgNOR has not yet been unequivocally established.

A series of genetic change has been described in the development of cancer.

In general, these changes seem to be of predictive value within defined tumor stages and it might be helpful to determine several genetic lesions within one tumor.

Very recently a new mechanism of carcinogenesis closely related to the hereditary nonpolyposis cancer syndrome (HNPCC) was detected. Due to mutations in mismatch repair genes (hMSH 2, hMLH 1, hPMS 1, 2) instabilities in simple repetitive genomic sequences occur, which are the genetic hallmark of most HNPCC tumors. This opens a new field to cancer prevention.

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 84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight 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

  • Aaltonen LA, Peltomäki P, Leach FS, Sistonen P, Pylkkänen L, Mecklin JP, Järvinen H, Powell SM, Jen J, Hamilton SR, Peterson GM, Kinzler KW, Vogelstein B, de la Chapelle A (1993) Clues of the pathogenesis of familial colorectal cancer. Science 260: 812–816

    CAS  Google Scholar 

  • Aaltonen LA, Peltomäki P, Mecklin JP, Järvinen H, Jass JR, Green JS, Lynch HT, Watson P, Tallqvist G, Juhola M, Sistonen P, Hamilton SR, Kinzler KW, Vogelstein B, de la Chapelle A (1994) Replication errors in benign and malignant tumors from hereditary nonpolyposis colorectal cancer patients. Cancer Res 54: 1645–1648

    CAS  Google Scholar 

  • Al-Sheneber I, Shibata H, Sampalis J, Jothy S (1993) Prognostic significance of prolif- erating cell nuclear antigen expression in colorectal cancer. Cancer 71: 1954–1959

    Article  PubMed  CAS  Google Scholar 

  • Baak JPA (1990) Mitosis counting in tumors. Hum Pathol 21: 683–685

    Article  PubMed  CAS  Google Scholar 

  • Baas I, Mulder J-W, Offerhaus G, Vogelstein B, Hamilton S (1994) An evaluation of six antibodies for immunohistochemistry of mutant p53 gene product in archival colorectal neoplasms. J Pathol 172: 5–12

    Article  PubMed  CAS  Google Scholar 

  • Benhattar J, Losi L, Chaubert P, Givel JC, Costa J (1993) Prognostic significance of kras mutations in colorectal carcinoma. Gastroenterology 104: 1044–1048

    PubMed  CAS  Google Scholar 

  • Bravo R, Frank R, Blundell PA, McDonald-Bravo H (1987) Cyclin/PCNA is the auxiliary protein of DNA polymerase alpha. Nature 236: 515–520

    Article  Google Scholar 

  • Brooks RF (1992) Regulation of the eukaryotic cell cycle. In: Hall PA, Levison DA, Wright NA (eds) Assessment of cell proliferation in clinical practice. Springer, Berlin Heidelberg New York, pp 1–26

    Google Scholar 

  • Burkart C (1994) Das Tumorsuppressorprotein p53. Dtsch Arztebl 91: 679–684

    Google Scholar 

  • Correa P, Shiao Y (1994) Phenotypic and genotypic events in gastric carcinogenesis. Cancer Res [Suppl] 54: 1941s - 1943s

    CAS  Google Scholar 

  • Crocker J, Nar P (1987) Nucleolar organizer regions in lymphomas. J Pathol 151: 111–118

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  • Fielding LP, Fenoglio-Preisser CM, Freedman LS (1992) The future of prognostic factors in outcome prediction of patients with cancer. Cancer 70: 2367–2377

    Article  PubMed  CAS  Google Scholar 

  • Finkelstein SD, Sayegh R, Christensen S, Swalsky PA (1993) Genotypic classification of colorectal adenocarcinoma. Cancer 71: 3827–3838

    Article  PubMed  CAS  Google Scholar 

  • Fishel R, Lescoe MK, Rao MRS, Copeland NG, Jenkins NA, Garber J, Kane M, Kolodner R (1993) The human mutator gene homologue MSH2 and its association with hereditary nonpolyposis colon cancer. Cell 75: 1027–1038

    Article  PubMed  CAS  Google Scholar 

  • Friedl W (1994) Familiäre adenomatöse Polyposis. Dtsch Arztebl 91(C):92–94 Graham D, Appelman H (1990) Crohn’s-like lymphoid reaction and colorectal carcinoma: a potential histologic prognosticator. Mod Pathol 3: 332–335

    Google Scholar 

  • Greenson JK, Isenhart CE, Rice R, Mojzisik C, Houchens D, Martin EW (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

    Google Scholar 

  • Griffiths A (1989) Silver-stained structures (AgNORs), their dependence on tissue fixation and absence of prognostic relevance in rectal adenocarcinoma. J Pathol 159: 121–127

    Article  PubMed  CAS  Google Scholar 

  • Hall PA, McKee PH, Menage HD, Dover R, Lane DP (1993) High levels of p53 protein in UV-irradiated normal skin. Oncogene 8: 203–207

    PubMed  CAS  Google Scholar 

  • Hamelin R, Laurent-Puig P, Olschwang S, Jego N, Asselain B, Remvikos Y, Girodet J, Salmon RJ, Thomas G (1994) Association of p53 mutations with short survival in colorectal cancer. Gastroenterology 106: 42–48

    PubMed  CAS  Google Scholar 

  • Hemming A, Davis N, Kluftinger A, Robinson B, Quenville N, Liseman B, LeRiche J (1992) Prognostic markers of colorectal cancer: an evaluation of DNA content, epidermal growth factor receptor and Ki-67. J Surg Oncol 51: 147–152

    Article  PubMed  CAS  Google Scholar 

  • Hermanek P, Guggenmoos-Holzmann I, Gall F (1989) Prognostic factors in rectal carcinoma. Dis Colon Rectum 32: 593–599

    Article  PubMed  CAS  Google Scholar 

  • Hollywood DP, Lemoine NR (1992) Growth factors, oncogenes and tumour suppressor genes. In: Hall PA, Levison DA, Wright NA (eds) Assessment of cell proliferation in clinical practice. Springer, Berlin Heidelberg New York, pp 27–43

    Google Scholar 

  • Iino H, Fukayama M, Maeda Y, Koike M, Mori T, Takahashi T, Kikuchi-Yanoshita R, Miyaki M, Mizuno S, Watanabe S (1994) Molecular genetics for clinical management of colorectal carcinoma. Cancer 73: 1324–1331

    Article  PubMed  CAS  Google Scholar 

  • Itoh F, Hinoda Y, Ohe M, Ohe Y, Ban T, Endo T, Imai K, Yachi A (1993) Decreased expression of DCC mRNA in human colorectal cancers. Int J Cancer 53: 260–263

    Article  PubMed  CAS  Google Scholar 

  • Jass JR, Love SB, Northover JMA (1987) A new prognostic classification of rectal cancer. Lancet 6: 1303–1306

    Article  Google Scholar 

  • Jen J, Kim H, Piatadosi S, Liu Z, Levitt R, Sistonen P, Kinzler K, Vogelstein B, Hamilton S (1994) Allelic loss of chromosome 18q and prognosis in colorectal cancer. N Engl J Med 331: 213–221

    Article  PubMed  CAS  Google Scholar 

  • Jino H, Fukayama M, Maeda Y, Koike M, Mori T, Takahashi T, Kikuchi-Yanoshita R, Miyaki M, Mizuno S, Watanabe S (1994) Molecular genetics for clinical management of colorectal carcinoma. 17p, 18q and 22q loss of heterozygosity and decreased DCC expression are correlated with the metastatic potential. Cancer 73: 1324–1331

    Article  Google Scholar 

  • Joyce W (1992) The prognostic value of nucleolar organiser regions in colorectal cancer. Ann R Coll Surg 74:172–6–176–7

    Google Scholar 

  • Key G, Becker M, Baron B, Duchrow M, Schlüter C, Flad H, Gerdes J (1993) New Ki67-equivalent murine monoclonal antibodies (MIB 1–3) generated against bacterially expressed parts of the Ki-67 cDNA containing three 62 base pair repetitive elements encoding for the Ki-67 epitope. Lab Invest 68: 629–636

    PubMed  CAS  Google Scholar 

  • Knudson AG (1985) Hereditary cancer, oncogenes, and antioncogenes. Cancer Res 45: 1437–1443

    PubMed  CAS  Google Scholar 

  • Kreipe H, Parwaresch R (1993) A closer look at the cell cycle. Virch Arch [A] 422: 341–343

    Article  CAS  Google Scholar 

  • Kreipe H, Wacker H, Heidebrecht J, Haas K, Hauberg M, Tiemann M, Parwaresch R (1993) Determination of the growth fraction in non-Hodgkin’s lymphomas by monoclonal antibody Ki-S5 directed against a formalin-resistant epitope of the Ki-67 antigen. Am J Pathol 142: 1689–1694

    PubMed  CAS  Google Scholar 

  • Kubota Y, Petras R, Easley K, Bauer T, Tubbs R, Fasio V (1992) Ki-67-determined growth fraction versus standard staging an grading parameters in colorectal carcinoma. Cancer 70: 2602–2609

    Article  PubMed  CAS  Google Scholar 

  • Kunkel TA (1993) Slippery DNA and diseases. Nature 365: 207–208

    Article  PubMed  CAS  Google Scholar 

  • Laurent-Puig P, Olschwang S, Delattre O, Remvikos Y, Asselain B, Melot T, Validire P, Muleris M, Girodet J, Salmon R, Thomas G (1992) Survival and acquired genetic alternations in colorectal cancer. Cancer 102: 1136–1141

    CAS  Google Scholar 

  • Linden M, Ma C, Kubus J, Brown R, Zarbo R (1993) Ki-67 and proliferating cell nuclear antigen tumor proliferative indices in DNA diploid colorectal adenocarcinoma. Am J Clin Pathol 100: 206–212

    PubMed  CAS  Google Scholar 

  • Lynch HT, Smyrk TC, Watson P, Lanspa SJ, Lynch JF, Lynch PM, Cavalieri RJ, Boland CR (1993) Genetics, natural history, tumor spectrum, and pathology of hereditary nonpolyposis colorectal cancer: an updated review. Gastroenterology 104: 1535–1549

    PubMed  CAS  Google Scholar 

  • Marshall CJ (1991) Tumor suppressor genes. Cell 64: 313–326

    Article  PubMed  CAS  Google Scholar 

  • Marx J (1993) New colon cancer gene discovered. Science 260: 751–752

    Article  PubMed  CAS  Google Scholar 

  • Mayer A, Takimoto M, Fritz E, Schellander G, Kofier K, Ludwig H (1993) The prognostic significance of proliferating cell nuclear antigen, epidermal growth factor receptor and mdr gene expression in colorectal cancer. Cancer 71: 2454–2460

    Article  PubMed  CAS  Google Scholar 

  • Miyahara M, Saito T, Kaketani K, Sato K, Kuwahara A, Shimoda K, Kobayashi M (1991) Clinical significance of ras p21 overexpression for patients with an advanced colorectal cancer. Dis Colon Rectum 34: 1097–1102

    Article  PubMed  CAS  Google Scholar 

  • Miyake S, Nagai K, Yosthino K, Oto M, Endo M, Yuasa Y (1994) Point mutations and allelic deletion of tumor suppressor gene DCC in human esophageal squamous cell carcinomas and their relation to metastasis. Cancer Res 54: 3007–3010

    PubMed  CAS  Google Scholar 

  • Motojima K, Urano T, Nagata Y, Shiku H, Tsunoda T, Kanematsu T (1991) Mutations in the Kirsten-ras oncogene are common but lack correlation with prognosis and tumour stage in human pancreatic carcinoma. Am J Gastroenterol 86: 1784–1788

    PubMed  CAS  Google Scholar 

  • Nicolaides NC, Papadopoulos N, Liu B, Wei YF, Carter KC, Ruben SM, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD, Venter JC, Dunlop MG, Hamilton SR, Peterson GM, de la Chapelle A, Vogelstein B, Kinzler KW (1994) Mutations of two PMS homologues in heredetary nonpolyposis colon cancer. Nature 371: 75–80

    CAS  Google Scholar 

  • Öfner D (1990) Silver-stained nucleolar organizer region proteins (Ag-NORs) as a predictor of prognosis in colonic cancer. J Pathol 162: 43–49

    Article  PubMed  Google Scholar 

  • Öfner D, Bankfalvi A, Riehemann K, Bier B, Schmid KW (1994) Wet autoclave pretreatment improves the visualisation of silver-stained nucleolar organizer regions associated proteins ( AgNORs) in routinely formalin-fixed and paraffin-embedded tissues. Mod Pathol 7: 946–951

    Google Scholar 

  • Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA, Haseltine WA, Fleischmann RD, Fraser CM, Adams MD, Venter JC, Hamilton SR, Peterson GM, Watson P, Lynch HT, Peltomäki P, Mecklin JP, de la Chapelle A, Kinzler KW, Vogelstein B (1994) Mutation of a mutL homolog in hereditary colon cancer. Science 263: 1625–1629

    CAS  Google Scholar 

  • Peltomäki P, Aaltonen LA, Sistonen P, Pylkkänen L, Mecklin JP, Järvinen H, Green JS, Jass JR, Weber JL, Leach FS, Petersen GM, Hamilton SR, de la Chapelle A, Vogelstein B (1993) Genetic mapping of a locus predisposing to human colorectal cancer. Science 260: 810–812

    Google Scholar 

  • Ponz de Leon M, Sant M, Micheli A, Sacchetti C, Di Gregorio C, Fante R (1992) Clinical and pathologic prognostic indicators in colorectal cancer. Cancer 69: 626–635

    Google Scholar 

  • Rayter Z, Surtees P, Tildsley G, Corbishley C (1992) The prognostic value of argyrophil nuclear organiser regions ( AgNORs) in colorectal cancer. Eur J Surg Oncol 18: 37–40

    Google Scholar 

  • Rhyu M-G, Park W-S, Jung Y-J, Choi S-W, Meltzer S (1994) Allelic deletions of MCC/ APC an p53 are frequent late events in human gastric carcinogenesis. Gastroenterology 106: 1584–1588

    PubMed  CAS  Google Scholar 

  • Rüschoff J (1992) Nucleolar organizer regions (NORs) in diagnostic tumor pathology. Fischer, Stuttgart

    Google Scholar 

  • Rüschoff J, Plate K, Contractor H, Kern H, Zimmermann R, Thomas C (1990) Evaluation of nucleolar organizer regions (NORs) by automatic image analysis: a contribution to standardization. J Pathol 161: 113–118

    Article  PubMed  Google Scholar 

  • Schlegel J, Bocker T, Zirngibl H, Hofstädter F, Rüschoff J (1995) Detection of microsatellite instability in human colorectal carcinomas using a non-radioactive PCR-based screening method. Virch Arch 426: 223–227

    CAS  Google Scholar 

  • Schlimok G, Funke I, Bock B, Schweiberer B, Witte J, Riethmüller G (1990) Epithelial tumor cells in bone marrow of patients with colorectal cancer: immunocytochemical detection, phenotypic characterization and prognostic significance. J Clin Oncol 8: 831–837

    PubMed  CAS  Google Scholar 

  • Schlimok G, Funke I, Pantel K, Strobel F, Lindemann F, Witte J, Riethmuller G (1991) Micrometastatic aspects of detection and prognostic significance. Eur J Cancer 27: 1461–1465

    Article  PubMed  CAS  Google Scholar 

  • Scott N, Sagar P, Stewart J, Blair GE, Dixon MF, Quirke P (1991) p53 in colorectal cancer: clinicopathological correlation and prognostic significance. Br J Cancer 63: 317–319

    Google Scholar 

  • Simon B, Weinel R, Höhne M, Watz J, Schmidt J, Körtner G, Arnold R (1994) Frequent alterations of the tumor suppressor genes p53 and DCC in human pancreatic carcinoma. Gastroenterology 106: 1645–1651

    PubMed  CAS  Google Scholar 

  • Soussi T, Legros Y, Lubin R, Ory K, Schlichtholz B (1994) Multifactorial analysis of p53 alteration in human cancer: a review. Int J Cancer 57: 1–9

    Article  PubMed  CAS  Google Scholar 

  • Starzynska T, Bromley M, Ghosh A, Stern PL (1992) Prognostic significance of p53 overexpression in gastric and colorectal carcinoma. Br J Cancer 66: 558–562

    Article  PubMed  CAS  Google Scholar 

  • Strand M, Prolla TA, Liskay RM, Petes TD (1993) Destabilization of tracts of simple repetitive DNA in yeast by mutations affecting DNA mismatch repair. Nature 365: 274–276

    Article  PubMed  CAS  Google Scholar 

  • Suchy B, Zietz Ch, Rabes HM (1992) K-ras point mutations in human colorectal carcinomas: relation to aneuploidy and metastasis. Int J Cancer 52: 30–33

    Article  PubMed  CAS  Google Scholar 

  • Taylor C, Shi S-R, Chaiwun B, Young L, Iman A, Cote R (1994) Strategies for improving the immunohistochemical staining of various intranuclear prognostic markers in formalin-paraffin sections: androgen receptor, estrogen receptor, progesterone receptor, p53 protein, proliferating cell nuclear antigen, and Ki-67 antigen revealed by antigen retrieval techniques. Hum Pathol 25: 263–270

    Article  PubMed  CAS  Google Scholar 

  • Thibodeau SN, Bren G, Schaid D (1993) Microsatellite instability in cancer of the proximal colon. Science 260: 816–819

    Article  PubMed  CAS  Google Scholar 

  • Union Internationale Contre le Cancer (UICC) (1993) TNM Atlas, 3rd edn. Springer, Berlin Heidelberg New York

    Google Scholar 

  • Vasen HFA, Mecklin JP, Meera Khan P, Lynch HT (1991) Hereditary non-polyposis colorectal cancer. Lancet 338: 877

    Article  Google Scholar 

  • Vogel P, Rüschoff J, Kümmel S, Zirngibl H, Hofstädter F, Hohenberger W (1995) Microscopic peritoneal seeding of gastrointestinal malignancies — first results of a prospective study. GUT 37 [Suppl 2]: A101

    Google Scholar 

  • Yamaguchi A, Nakagawara G, Kuroska Y, Nishimura G, Yonemura Y, Miyazaki J (1993) p53 immunoreaction in endoscopic biopsy specimens of colorectal cancer, and its prognostic significance. Br J Cancer 68: 399–402

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Institute of Pathology, University of Regensburg, Franz-Josef-Strauss-Allee 11, 93042, Regensburg, Germany

    J. Rüschoff, T. Bocker & J. Schlegel

  2. Department of Surgery, University of Regensburg, 93042, Regensburg, Germany

    P. Vogel

Authors
  1. J. Rüschoff
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. T. Bocker
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. P. Vogel
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. J. Schlegel
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Fachbereich Humanmedizin, Univ.-Klinikum Benjamin Franklin, Medizinische Klinik und Poliklinik, Schwerpunkt Hämatologie und Onkologie, Freie Universität Berlin, Hindenburgdamm 30, 12200, Berlin, Germany

    Ernst-D. Kreuser

  2. Robert-Rössle Klinik am Max-Delbrück-Centrum, Humboldt-Universität, Lindenberger Weg 80, 13122, Berlin, Germany

    P. M. Schlag

Rights and permissions

Reprints and permissions

Copyright information

© 1996 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Rüschoff, J., Bocker, T., Vogel, P., Schlegel, J. (1996). Prognostic Significance of Molecular Biological and Immunohistological Parameters in Gastrointestinal Carcinomas. In: Kreuser, ED., Schlag, P.M. (eds) New Perspectives in Molecular and Clinical Management of Gastrointestinal Tumors. Recent Results in Cancer Research, vol 142. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-80035-1_6

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-80035-1_6

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-80037-5

  • Online ISBN: 978-3-642-80035-1

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation