Increased expression of integrin beta1 is a poor prognostic factor in small-cell lung cancer

The purpose of this study was to investigate the possible association between the expression of integrin beta1 and response to chemotherapy and survival in patients with small cell lung cancer (SCLC). One-hundred and four patients with SCLC, who had received an initial course of chemotherapy between February 1989 and July 1999, were entered into the study. There were 91 males and 13 females, with a median age of 65 years (range 40-85 years). The clinical stage of the tumors was recorded as limited disease in 43 patients and extensive disease in 61. Each patient received a full-dose of combination chemotherapy. Transbroncheal biopsy specimens of tumors obtained before chemotherapy were subjected to immunostaining for integrin beta1. Twenty-nine patients could not be evaluated for integrin beta1 immunostaining, because the tissue samples had been crushed during the biopsy procedure. Fifty-three patients had tumors with < or = 25% integrin beta1-positive cells and 22 patients had tumor with > 25% integrin beta1-positive cells. Among 75 patients whose biopsy specimens were evaluable for integrin beta1, the overall response rate to chemotherapy was 87%. When the relationship between integrin beta1 expression and tumor response to chemotherapy was considered, 17 out of 22 patients with high expression of integrin beta1 and 48 out of 53 patients with low expression of integrin beta1 showed tumor response, although the resistance rate in patients with high expression of integrin beta1 was over twice that of patients with low expression of integrin beta1 (23% vs. 9%, respectively). By comparison, the overall survival of patients with high expression of integrin beta1 (n = 22) was significantly worse than that of individuals whose tumors had low expression of integrin beta1 (n = 53; log-rank test, p=0.043; Wilcoxon test, p=0.049). The association between survival and prognostic factors was examined by multivariate regression analysis; clinical stage and integrin beta1 were found to be independent factors (p = 0.018 andp = 0.041, respectively). In conclusion, the high expression of integrin beta1 in tumor cells is a poorprognostic factor in patients with SCLC.