Tumor angiogenesis and biologic markers in resected stage I NSCLC

Abstract

OBJECTIVE: Microvessel count (MC), as a measure of tumor angiogenesis, has been shown to be significantly correlated with metastatic disease incutaneous, mammary, prostatic, head and neck cancer. We have previously assessed the role of intensity of angiogenesis as predictor of metastasisin surgically resected T1N0M0 NSCLC. We needed to confirm its value, in a prospective larger study on Stage I NSCLC, before its utilization as aprognostic tool for further clinical investigations. METHODS: In the present report we prospectively investigated 227 patients (206 males, 21 females; median age 65 years) with Stage I NSCLC treated only by radical surgery between March 1991 and December 1994 with utmost care for some biological characteristics (proliferative activity, the blood vessel invasion, angiogenesis and the p53 protein expression). RESULTS: The operative procedures consisted of 62 pneumonectomies, 148 lobectomies and 17 segmentectomies or wedge resections. With a median follow-up of 36 months (range 15-60), eighty patients have already experienced a local (n = 22) or systemic (n = 58) relapse. Univariate analysis revealed that T factor (T1 versus T2)(P = 0.008) and angiogenesis count (< or = versus > median, 17) (P = 0.0006) were significant predictors of survival. The same variables were also significant predictors of long Disease Free Survival (P = 0.006 and P = 0.004, respectively). On multivariate analysis, however, only the microvessel count retained its level of prognostic significance as regards both overall (P < 0.01) and disease-free survival (P < 0.01). CONCLUSIONS: The present study corroborates therole of angiogenesis in the metastatic spread of NSCLC and emphasizes itsvalue in the identification of patients in whom surgery should be supplemented by systemic treatment.