EVALUATION OF EPIDERMAL GROWTH FACTOR-RELATED GROWTH-FACTORS AND RECEPTORS AND OF NEOANGIOGENESIS IN COMPLETELY RESECTED STAGE I-IIIA NON-SMALL-CELL LUNG-CANCER - AMPHIREGULIN AND MICROVESSEL COUNT ARE INDEPENDENT PROGNOSTIC INDICATORS OF SURVIVAL

We have determined the expression of transforming growth factor alpha (TGF alpha), amphiregulin (AR), CRIPTO, the epidermal growth factor re ceptor (EGFR), erbB-2, erbB-3, and tumor angiogenesis in a series of 1 95 patients with stage I-IIIA non-small cell lung cancer (NSCLC) treat ed with radical surgery to define their usefulness as prognostic indic ators of survival. A variable degree of specific staining in cancer ce lls was observed for the three growth factors and for the three growth factor receptors in the majority of NSCLC patients. A statistically s ignificant association between overexpression of TGF alpha, AR, and CR IPTO was observed. Enhanced expression of AR was significantly correla ted with enhanced expression of erbB-2 and advanced T-stage. A direct association was also detected for overexpression of TGF alpha and of E rbB-2 off erbB-3, respectively. Sex, tumor size, nodal status, stage, microvessel count, as a measure of neovascularization, and AR overexpr ession significantly correlated with overall survival at univariate an alysis. In a Cox multivariate analysis, the only characteristics with an independent prognostic effect on OAS were microvessel count [relati ve hazard (RH), 6.61; P < 0.00001), nodal status (RH, 1.59; P = 0.0013 ), and AR overexpression (RH, 1.72; P = 0.02). These results suggest t hat evaluation of neoangiogenesis and of certain growth factors, such as AR, can be useful in addition to conventional pathological staging to select high-risk NSCLC patients who may benefit from postsurgical s ystemic therapies.