HercepTest: HER2 expression and gene amplification in non-small cell lung cancer

HER2 is an erbB/HER type I tyrosine kinase receptor that is frequently over -expressed in malignant epithelial tumours, Herceptin, a humanised mouse mo noclonal antibody to HER2, is proven therapeutically in the management of m etastatic breast cancer, significantly prolonging survival when combined wi th cytotoxic chemotherapeutic agents, Immunohistochemical studies suggest t hat non-small-cell lung cancer (NSCLC) tumours may over-express HER2, Our a im was to evaluate HER2 gene amplification and semi-quantitative immuno-exp ression in NSCLC. A total of 344 NSCLC cases were immunostained far HER2 ex pression in 2 centres using the HercepTest. Fluorescence in situ hybridisat ion (FISH) analysis for HER2 gene amplification was performed on most posit ive cases and a subset of negative cases. Fifteen cases (4.3%) demonstrated 2+ or 3+ membranous HER2 immuno-expression. There was no correlation betwe en immuno-expression and tumour histology or grade. Tumours from higher-sta ge disease were more often HercepTest-positive (p < 0.001). All 4 HercepTes t 3(+) cases demonstrated gene amplification, One of the 5 2+ cases tested for gene amplification showed areas of borderline amplification and areas o f polyploidy. None of the 19 HercepTest-negative cases demonstrated gene am plification or polyploidy (p < 0.001). Gene amplification was demonstrated in all HercepTest 3+ scoring NSCLC cases. Unlike breast cancer, gene amplif ication and HER2 protein over-expression assessed by the HercepTest appeare d to be uncommon in NSCLC. Herceptin may therefore target only a small prop ortion of NSCLC tumours and be of limited clinical value in this disease, p articularly in the adjuvant setting, (C) 2001 Wiley-Liss, Inc.