p185^neu Expression in Human Lung Adenocarcinomas Predicts Shortened Survival

Abstract

p185^neu is the protein product of the HER2/neu protooncogene. This protein has characteristics of a tyrosine kinase growth factor receptor and is postulated to be important in human carcinogenesis. To define the significance of the expression of this protein in human non-small cell lung cancer, 55 tumors from patients with squamous cell carcinoma (16), adenocarcinoma (29), or large cell carcinoma (10) of the lung were examined for p185^neu using immunohistological methods. Five of 16 squamous cell carcinomas and 10 of 29 adenocarcinomas were found to overexpress p185^neu relative to levels of expression seen in uninvolved bronchiolar epithelium. For the adenocarcinomas, p185^neu expression was associated with older age (66.6 ± 10.1 versus 57.5 ± 10.8 years) (P = 0.04) and shortened survival (83.7 ± 94.1 versus 188.5 ± 120 weeks) (P = 0.01). In this group, using Cox's multivariate survival analysis, p185^neu expression was found to be a significant determinant of survival (P = 0.04) even after accounting for the effect of tumor stage. For the squamous cell carcinomas, p185^neu expression was not correlated with any of our clinicopathological parameters. Our findings indicate that non-small cell lung cancers which express p185^neu do so at levels higher than that found in normal bronchiolar epithelium, and expression in adenocarcinomas of the lung is independently associated with diminished survival intervals.