Evaluation of HER-2/neu gene amplification and protein expression in non-small cell lung carcinomas

• Published in: British journal of cancer Vol. 86; no. 9; pp. 1449 - 1456
• Main Authors: HIRSCH, F. R, VARELLA-GARCIA, M, FRANKLIN, W. A, VEVE, R, CHEN, L, HELFRICH, B, ZENG, C, BARON, A, BUNN, P. A
• Format: Journal Article
• Language: English
• Published: Basingstoke Nature Publishing Group 06.05.2002
• Subjects: Aged; Biological and medical sciences; Breast cancer; Cancer research; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - pathology; Female; Gene Amplification; Gene Expression Regulation, Neoplastic; Health sciences; Humans; Immunohistochemistry; In Situ Hybridization, Fluorescence; Kinases; Lung cancer; Lung Neoplasms - genetics; Lung Neoplasms - pathology; Male; Medical prognosis; Medical research; Medical sciences; Microscopy, Fluorescence; Middle Aged; Molecular and Cellular Pathology; Monoclonal antibodies; Pneumology; Preventive medicine; Prognosis; Protein expression; Proteins; Receptor, ErbB-2 - biosynthesis; Response rates; Survival Analysis; Tumors; Tumors of the respiratory system and mediastinum; United States > US; Colorado; Human; Lung disease; Prognosis; Respiratory disease; Gene overexpression; Malignant tumor; Bronchopulmonary; Gene amplification; C-Onc gene; Bronchus disease; Genetics; Protooncogene; Non small cell carcinoma
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/sj.bjc.6600286

HER-2/neu gene amplification and cell surface overexpression are important factors in breast cancer for prognosis and prediction of sensitivity to anti-HER-2/neu monoclonal antibody therapy. In lung cancer, the clinical significance of HER-2/neu expression is currently under evaluation. We investigated 238 non-small lung carcinomas for HER-2/neu protein overexpression by immunohistochemistry using the HercepTest. We found 2+ or 3+ overexpression in 39 patients (16%), including 35% in adenocarcinomas and 20% in large cell carcinomas, but only 1% of squamous cell carcinomas. Marked (3+) overexpression was uncommon (4%). The association between protein expression and gene copy number per cell, as determined by fluorescence in situ hybridisation assay, was investigated in 51 of these NSCLC tumours. Twenty-seven tumours (53%) were negative by both tests. Marked (3+) protein expression and gene amplification were present in only 4% of samples. In 11 tumours (21%), gene gain was accompanied by chromosomal aneusomy and did not result in high protein levels while in 7 (14%) the score 2+ was associated with maximum number of signals per cell <9. The prognostic implication of HER-2/neu protein expression was studied in 187 surgically resected tumours. No statistical difference in survival was observed comparing patients with positive (2+/3+) and negative tumours (0/1+), although 3+ patients showed a tendency to shorter survival. The therapeutic implications of protein expression and gene amplification in lung cancer need to be examined in prospective clinical trials.