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Familial Cancer

, Volume 1, Issue 2, pp 87–93 | Cite as

The reliability of immunohistochemistry as a prescreening method for the diagnosis of hereditary nonpolyposis colorectal cancer (HNPCC) – Results of an international collaborative study

  • Wolfram Müller
  • Lawrence J. Burgart
  • Ruth Krause-Paulus
  • Stephen N. Thibodeau
  • M. Almeida
  • T. Brocker Edmonston
  • C. R. Boland
  • C. Sutter
  • J. R. Jass
  • A. Lindblom
  • J. Lubinski
  • K. MacDermot
  • D. S. A. Sanders
  • H. Morreau
  • A. Müller
  • C. Oliani
  • T. Orntoft
  • M. Ponz De Leon
  • C. Rosty
  • M. Rodriguez-Bigas
  • J. Rüschoff
  • A. Ruszkiewicz
  • J. Sabourin
  • R. Salovaara
  • Gabriela Möslein
Article

Abstract

Hereditary nonpolyposis colorectal cancer syndrome (HNPCC) is an autosomal dominant condition accounting for 2–5% of all colorectal carcinomas as well as a small subset of endometrial, upper urinary tract and other gastrointestinal cancers. An assay to detect the underlying defect in HNPCC, inactivation of a DNA mismatch repair enzyme, would be useful in identifying HNPCC probands. Monoclonal antibodies against hMLH1 and hMSH2, two DNA mismatch repair proteins which account for most HNPCC cancers, are commercially available. This study sought to investigate the potential utility of these antibodies in determining the expression status of these proteins in paraffin-embedded formalin-fixed tissue and to identify key technical protocol components associated with successful staining. A set of 20 colorectal carcinoma cases of known hMLH1 and hMSH2 mutation and expression status underwent immunoperoxidase staining at multiple institutions, each of which used their own technical protocol. Staining for hMSH2 was successful in most laboratories while staining for hMLH1 proved problematic in multiple labs. However, a significant minority of laboratories demonstrated excellent results including high discriminatory power with both monoclonal antibodies. These laboratories appropriately identified hMLH1 or hMSH2 inactivation with high sensitivity and specificity. The key protocol point associated with successful staining was an antigen retrieval step involving heat treatment and either EDTA or citrate buffer. This study demonstrates the potential utility of immunohistochemistry in detecting HNPCC probands and identifies key technical components for successful staining.

hMLH1 hMSH2 HNPCC immunohistochemistry mismatch repair 

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Copyright information

© Kluwer Academic Publishers 2001

Authors and Affiliations

  • Wolfram Müller
    • 1
  • Lawrence J. Burgart
    • 2
  • Ruth Krause-Paulus
    • 3
  • Stephen N. Thibodeau
    • 4
  • M. Almeida
    • 5
  • T. Brocker Edmonston
    • 6
  • C. R. Boland
    • 7
  • C. Sutter
    • 8
  • J. R. Jass
    • 9
  • A. Lindblom
    • 10
  • J. Lubinski
    • 11
  • K. MacDermot
    • 12
  • D. S. A. Sanders
    • 13
  • H. Morreau
    • 14
  • A. Müller
    • 15
  • C. Oliani
    • 16
  • T. Orntoft
    • 17
  • M. Ponz De Leon
    • 18
  • C. Rosty
    • 19
  • M. Rodriguez-Bigas
    • 20
  • J. Rüschoff
    • 21
  • A. Ruszkiewicz
    • 22
  • J. Sabourin
    • 23
  • R. Salovaara
    • 24
  • Gabriela Möslein
    • 3
  1. 1.Institute of PathologyHeinrich Heine UniversityDüsseldorfGermany
  2. 2.Department of PathologyMayo ClinicRochesterUSA
  3. 3.Department of SurgeryHeinrich Heine UniversityDüsseldorfGermany
  4. 4.Department of Molecular GeneticsMayo ClinicRochesterUSA
  5. 5.Northern Genetics CenterUniversity of NewcastleNewcastle upon TyneUK
  6. 6.Kimmel Cancer InstituteThomas Jefferson UniversityPhiladelphiaUSA
  7. 7.University of CaliforniaSan DiegoUSA
  8. 8.Department of Surgery, Division of Molecular Diagnostics & TherapyUniversity of HeidelbergGermany
  9. 9.Department of Pathology, Graduate Medical SchoolUniversity of QueenslandAustralia
  10. 10.Department of Clinical GeneticsKarolinska HospitalStockholmSweden
  11. 11.Hereditary Cancer CenterPomerian Medical UniversitySzczecinPoland
  12. 12.Department of Clinical GeneticsRoyal Free HospitalLondonUK
  13. 13.Department of PathologyThe Medical School, EdgbastonBirminghamUK
  14. 14.Department of PathologyUniversity of LeidenThe Netherlands
  15. 15.Department of SurgeryUniversity of GöttingenGermany
  16. 16.Division of OncologyOspedale Civile MaggioreVeronaItaly
  17. 17.Department of Clinical BiochemistryAarhus UniversityDenmark
  18. 18.Department of Medicine IIIUniversity ModenaModenaItaly
  19. 19.Laboratory of Molecular Toxicology U490University René DescartesParis VFrance
  20. 20.Department of Surgery OncologyRoswell Park Cancer Inst.USA
  21. 21.Department of PathologyStädt. Klinikum KasselKasselGermany
  22. 22.Division of Tissue PathologyInstitute of Medical + Veterinary ScienceAdelaideAustralia
  23. 23.Department of PathologyInstitute Gustav RoussyVillejuif CedesFrance
  24. 24.Department of Medical Genetics and PathologyUniversity of HelsinkiHelsinkiFinland

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