Simultaneous detection of HER2/neu gene amplification and protein overexpression in paraffin-embedded breast cancer

Lottner, C and Schwarz, S and Diermeier, S and Hartmann, A and Knuechel, R and Hofstaedter, F and Brockhoff, G (2005) Simultaneous detection of HER2/neu gene amplification and protein overexpression in paraffin-embedded breast cancer. JOURNAL OF PATHOLOGY, 205 (5). pp. 577-584. ISSN 0022-3417, 1096-9896

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Abstract

The determination of HER2/neu status in breast carcinomas has become essential for the selection of breast cancer patients for Herceptin therapy. Herceptin treatment is used in patients with metastatic breast carcinoma with HER2/neu protein overexpression detected by immunohistochemistry (IHC) or gene amplification analysed by fluorescence in situ hybridization (FISH). A multiparametric fluorescent approach based on the simultaneous detection of HER2/neu gene amplification and protein expression was established to increase the accuracy, and to improve the reproducibility, of HER2/neu diagnostics. Based on four paraffin-embedded breast cancer cell lines, a combined fluorescent immunostaining (FIHC) and FISH method was developed by using the PathVysion HER2 DNA Probe Kit (VYSIS) and the polyclonal antibody from the HercepTest (DAKO). Diagnostic applicability was documented on 215 formalin-fixed primary breast carcinomas. Criteria for immunofluorescence quantification were chosen by analogy with the FDA-approved HercepTest scoring, ranging from 0 to 3+. There was 97.7% concordance between conventional HIC and fluorescence HIC. The FISH data resulting from the multiparametric approach did not differ from conventional FISH. Breast carcinomas with HER2/neu protein overexpression and simultaneous gene amplification were detected with 100% sensitivity. In addition, five of the 215 cases (2.3%) had HER2/neu gene amplification without protein overexpression. The main advantage of this novel approach is that polysomy, aneuploidy, gene amplification, and protein content can be analysed simultaneously in the same cell. Copyright (c) 2005 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

Item Type: Article
Uncontrolled Keywords: IN-SITU HYBRIDIZATION; ARCHIVAL TISSUE SAMPLES; IMMUNOHISTOCHEMICAL ASSAY; HER-2/NEU; ONCOGENE; CARCINOMA; TUMORS; TRASTUZUMAB; SENSITIVITY; PROGRESSION; HER2/neu; immunohistochemistry; fluorescence immunohistochemistry; fluorescence in situ hybridization; FISH; breast cancer; simultaneous detection
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Pathologie
Depositing User: Dr. Gernot Deinzer
Date Deposited: 18 May 2021 07:37
Last Modified: 18 May 2021 07:37
URI: https://pred.uni-regensburg.de/id/eprint/36315

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