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Correlation between immunohistochemistry (HercepTest) and fluorescence in situ hybridization (FISH) for HER‐2 in 426 breast carcinomas from 37 centres
Author(s) -
Dowsett M,
Bartlett J,
Ellis IO,
Salter J,
Hills M,
Mallon E,
Watters AD,
Cooke T,
Paish C,
Wencyk PM,
Pinder SE
Publication year - 2003
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.1313
Subject(s) - immunohistochemistry , fluorescence in situ hybridization , concordance , trastuzumab , breast cancer , fish <actinopterygii> , medicine , in situ hybridization , pathology , chromosome 17 (human) , in situ hybridisation , cancer , oncology , biology , chromosome , gene , gene expression , biochemistry , fishery
Accurate diagnostic assessment of HER‐2 is essential for the appropriate application of the humanized anti‐HER‐2 monoclonal antibody trastuzumab (Herceptin) to the treatment of patients with metastatic breast cancer. The diagnostic test needs to be applicable to archival, fixed tissue removed at excision, in many cases several years earlier. We compared the assessment of HER‐2 by immunohistochemistry (IHC; HercepTest) and fluorescence in situ hybridization (FISH) in 426 breast carcinomas from patients being considered for trastuzumab therapy. The tumours were tested in three reference centres having been sent in from 37 hospitals. Only 2/270 (0.7%) IHC 0/1+ tumours were FISH positive. Six of 102 (5.9%) IHC 3+ tumours were FISH negative. Five of the six had between 1.75 and 2.0 HER‐2 gene copies per chromosome 17 and the sixth had multiple copies of chromosome 17. Thirteen per cent of tumours were IHC 2+ and overall 48% of these were FISH positive but this proportion varied markedly between the centres. Sixty IHC‐stained slides selected to be enriched with 2+ cases were circulated between the three laboratories and scored. There were 20 cases in which there was some discordance in scoring. Consideration of the FISH score in these cases led to concordance in the designation of positivity/negativity in 19 of these 20 cases. These data support an algorithm in which FISH testing is restricted to IHC 2+ tumours in reference centres. The results may not extrapolate to laboratories with less experience or using different methodologies. Copyright © 2003 John Wiley & Sons, Ltd.