Tumour necrosis factor- α and transforming growth factor- β are significantly associated with better prognosis in non-small cell lung carcinoma: putative relation with BCL -2-mediated neovascularization

Recent in vivo and in vitro studies have demonstrated a wide spectrum of biologic activities of cytokines in the pathogenesis and progression of malignancy. Tumour necrosis factor alpha (TNF-α) and transforming growth factor beta (TGF-β) have emerged as two of the many host-derived mediators that seem to interfere with both antiproliferative and tumorigenic effects in malignant tumours including lung cancer. However, their association with tumour prognosis or prognostic factors has not yet been completely clarified. In this study, we assessed TNF-α and TGF-β mRNA expression by RT-PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-α and TGF-β mRNA in 55.74% and 45.9% of cases, respectively. We also evaluated the expression of the two distinct transmembrane TNF receptors. TNFR-I and TNFR-II, with a PCR-positive signal in 70.49% and 65.57% of cases, respectively. In 49 of the 61 cases, we evaluated the prognostic impact of the two growth-inhibiting factors using the Kaplan–Meier analysis. In the univariate analysis patients without nodal metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF-α and TGF-β positive cancers (P = 0.01 and P = 0.03) showed a favourable prognosis in terms of overall survival. Since our previous studies demonstrated a significant association between NSCLC behaviour, neoangiogenesis and bcl -2 expression, we investigated the putative relation between TNF-α and TGF-β on the one hand, and vascular count (as a measure of tumour angiogenesis) and bcl -2 protein expression, on the other hand. Our results showed a significant direct association between TNF-α and bcl -2 (P = 0.05) and an inverse association between TNF-α and microvessel count (P = 0.03). Moreover, as previously demonstrated, we observed a significant inverse correlation between bcl -2 protein expression and vascular count (P = 0.05), suggesting that the favourable effect of TNF-α on clinical outcome may be related to a bcl -2-mediated low neovascular development. © 2000 Cancer Research Campaign