Role of different immunostaining patterns in HercepTest interpretation and criteria for gene amplification as determined by fluorescence in situ hybridization

Geza Acs, Lynn Wang, Puthiyaveettil N. Raghunath, Marilyn A. Salscheider, Paul J. Zhang

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

Abstract

Immunohistochemical (IHC) detection of HER-Z overexpression by HercepTest on paraffin sections has been proposed for selecting patients with metastatic breast carcinoma for Herceptin therapy. Interpretation of intermediate (2+) reactivity could be subjective and has been shown to have low concordance with fluorescence in situ hybridization (FISH). FISH assay for gene amplification (GA) has been used as a confirmatory test in equivocal cases with different criteria judging gene amplification. A wide range of discordance between IHC and FISH has been reported in the literature, with ongoing debate about which assay is more accurate for HER-Z test. Little attention has been paid to the role of different criteria in judging protein overexpression on IHC and GA on FISH. We evaluated HER-Z overexpression and GA by IHC (HercepTest) and FISH (PathVysion), respectively, on paraffin sections of 142 primary breast carcinomas. For the HercepTest, in addition to scoring guidelines proposed by the manufacturer, scoring systems taking into consideration the pattern of membranous staining and staining in benign epithelium were also evaluated. For the FISH assay, the ratios of HER-Z:CEP 17, HER-Z:cell, and CEP 17:cell were used to evaluate the impact of the different criteria for determining GA. HER-Z overexpression was detected in 53 (37.3%), 48 (33.8%), and 36 (25.4%) cases according to the HercepTest, normal epithelium-modified, and pattern-modified scoring systems, respectively. The HER-Z gene was considered amplified in 41 (28.9%), 37 (26.1%), and 34 (23.9%) cases according to the HER-Z:cell criteria, HER-Z:CEP 17 criteria, and the combined criteria, respectively. Our results suggest that a high concordance (95.8%) between HER-Z overexpression and GA can be achieved by using more stringent pattern-modified criteria for judging protein overexpression and combined criteria for GA.

Original languageEnglish
Pages (from-to)222-229
Number of pages8
JournalApplied Immunohistochemistry and Molecular Morphology
Volume11
Issue number3
DOIs
StatePublished - Sep 2003

Keywords

  • Breast carcinoma
  • FISH
  • HER-Z/neu
  • HercepTest
  • Immunohistochemistry

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