Premium
Herceptest: Her2 expression and gene amplification in non‐small cell lung cancer
Author(s) -
Cox G.,
Vyberg M.,
Melgaard B.,
Askaa J.,
Oster A.,
O'Byrne K.J.
Publication year - 2001
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.1214
Subject(s) - gene duplication , breast cancer , lung cancer , cancer research , fluorescence in situ hybridization , carcinoma , immunohistochemistry , biology , medicine , cancer , pathology , oncology , gene , chromosome , biochemistry
HER2 is an erbB/HER type 1 tyrosine kinase receptor that is frequently over‐expressed in malignant epithelial tumours. Herceptin, a humanised mouse monoclonal antibody to HER2, is proven therapeutically in the management of metastatic breast cancer, significantly prolonging survival when combined with cytotoxic chemotherapeutic agents. Immunohistochemical studies suggest that non‐small‐cell lung cancer (NSCLC) tumours may over‐express HER2. Our aim was to evaluate HER2 gene amplification and semi‐quantitative immuno‐expression in NSCLC. A total of 344 NSCLC cases were immunostained for HER2 expression in 2 centres using the HercepTest. Fluorescence in situ hybridisation (FISH) analysis for HER2 gene amplification was performed on most positive cases and a subset of negative cases. Fifteen cases (4.3%) demonstrated 2+ or 3+ membranous HER2 immuno‐expression. There was no correlation between immuno‐expression and tumour histology or grade. Tumours from higher‐stage disease were more often HercepTest‐positive ( p < 0.001). All 4 HercepTest 3 + cases demonstrated gene amplification. One of the 5 2+ cases tested for gene amplification showed areas of borderline amplification and areas of polyploidy. None of the 19 HercepTest‐negative cases demonstrated gene amplification or polyploidy ( p < 0.001). Gene amplification was demonstrated in all HercepTest 3+ scoring NSCLC cases. Unlike breast cancer, gene amplification and HER2 protein over‐expression assessed by the HercepTest appeared to be uncommon in NSCLC. Herceptin may therefore target only a small proportion of NSCLC tumours and be of limited clinical value in this disease, particularly in the adjuvant setting. © 2001 Wiley‐Liss, Inc.