HER‐2/neuoverexpression in patients with radically resected nonsmall cell lung carcinoma

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Abstract
BACKGROUND: Using immunohistochemistry, the authors prospectively investigated the expression of HER‐2/neuprotein in radically resected specimens of nonsmall cell lung carcinoma (NSCLC) and evaluated its impact on long‐term prognosis.METHODS: Between January 1991 and February 1992, surgical specimens from 130 consecutive patients who underwent radical resection for NSCLC (60 squamous cell carcinoma, 48 adenocarcinoma cases, and 22 large cell carcinomas) and that were staged (according to the TNM staging system) pathologically as Stage I (41 cases [ 32%]), Stage II (37 cases [28%]), and Stage IIIA (52 cases [40%]) were investigated for the expression of HER‐2/neuusing an avidin‐biotin complex immunohistochemical technique. A semiquantitative four‐stage grading system was used (0%, 1–5%, 6–20%, and > 20% positive cells) and an average number of 1500 cells/section was considered. Data were correlated with clinical and pathologic variables.RESULTS: Normal bronchial tissue was found to be completely negative for HER‐2/neuexpression whereas 21 of the 130 tumor specimens (16%) were positive (range 1–> 20%). HER‐2/neupositivity did not appear to differ significantly among pathologic stages and histotypes. Using a predetermined cutoff value of 5% positive cells, 15 tumor specimens (12%) were found to be above this value. The median survival time (85 weeks vs. 179 weeks) and overall survival rate were significantly lower in patients with > 5% HER‐2/neu‐positive tumors (hazard ratio for the group with > 5% positive cells: 2.94, 95% confidence interval, 1.62–5.34;P< 0.0004). On multivariate analysis, HER‐2/neuand extent of tumor emerged as independent factors for disease‐related mortality.CONCLUSIONS: In NSCLC, the negative impact of HER‐2/neuoverexpression on survival was maintained in the long‐term follow‐up of radically resected patients. HER‐2/neuoverexpression may be a valuable prognostic factor as well as a potential target for biologic therapies. Cancer 2002;94:2669–74. © 2002 American Cancer Society.DOI 10.1002/cncr.10531