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

被引：80

作者：

Müller W. ^{[1
]}

Burgart L.J. ^{[2
]}

Krause-Paulus R. ^{[3
]}

Thibodeau S.N. ^{[4
]}

Almeida M. ^{[5
]}

Edmonston T.B. ^{[6
]}

Boland C.R. ^{[7
]}

Sutter C. ^{[8
]}

Jass J.R. ^{[9
]}

Lindblom A. ^{[10
]}

Lubinski J. ^{[11
]}

Macdermot K. ^{[12
]}

Sanders D.S.A. ^{[13
]}

Morreau H. ^{[14
]}

Müller A. ^{[15
]}

Oliani C. ^{[16
]}

Orntoft T. ^{[17
]}

De Leon M.P. ^{[18
]}

Rosty C. ^{[19
]}

Rodriguez-Bigas M. ^{[20
]}

Rüschoff J. ^{[21
]}

Ruszkiewicz A. ^{[22
]}

Sabourin J. ^{[23
]}

Salovaara R. ^{[24
]}

Möslein G. ^{[3
]}

机构：

[1] Institute of Pathology, Heinrich Heine University, Düsseldorf

[2] Department of Pathology, Mayo Clinic, Rochester

[3] Department of Surgery, Heinrich Heine University, Düsseldorf

[4] Department of Molecular Genetics, Mayo Clinic, Rochester, MN

[5] Northern Genetics Center, University of Newcastle, Newcastle upon Tyne

[6] Kimmel Cancer Institute, Thomas Jefferson University, Philadelphia

[7] University of California, San Diego, CA

[8] University of Heidelberg, Department of Surgery, Division of Molecular Diagnostics and Therapy

[9] Department of Pathology, Graduate Medical School, University of Queensland

[10] Department of Clinical Genetics, Karolinska Hospital, Stockholm

[11] Pomerian Medical University, Hereditary Cancer Center, Szczecin

[12] Department of Clinical Genetics, Royal Free Hospital, London

[13] Department of Pathology, Medical School, Edgbaston

[14] Department of Pathology, University of Leiden

[15] Department of Surgery, University of Göttingen

[16] Division of Oncology, Ospedale Civile Maggiore, Verona

[17] Department of Clinical Biochemistry, Aarhus University

[18] Department of Medicine III, University Modena, Modena

[19] Laboratory of Molecular Toxicology U490, University René Descartes, Paris V

[20] Department of Surgery Oncology, Roswell Park Cancer Inst., New York, NY

[21] Department of Pathology, Städt. Klinikum Kassel, Kassel

[22] Institute of Medical + Veterinary Science, Division of Tissue Pathology, Rundle Mall, Adelaide

[23] Institute Gustav Roussy, Department of Pathology, Villejuif Cedes

[24] Department of Medical Genetics and Pathology, University of Helsinki, Helsinki

来源：

Familial Cancer | 2001年 / 1卷 / 2期

关键词：

HMLH1; HMSH2; HNPCC; Immunohistochemistry; Mismatch repair;

D O I：

10.1023/A:1013840907881

中图分类号：

学科分类号：

摘要：

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.

引用

页码：87 / 92

页数：5

共 30 条

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