Tumour necrosis factor-alpha and transforming growth factor-beta 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 bi ologic activities of cytokines in the pathogenesis and progression of malig nancy. Tumour necrosis factor alpha (TNF-alpha) and transforming growth fac tor beta (TGF-beta) 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 clarifi ed. In this study, we assessed TNF-alpha and TGF-beta mRNA expression by RT -PCR technique in 61 NSCLC samples, demonstrating the presence of TNF-alpha and TGF-beta mRNA in 55.74% and 45.9% of cases, respectively. We also eval uated 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, re spectively. In 49 of the 61 cases, we evaluated the prognostic impact of th e two growth-inhibiting factors using the Kaplan-Meier analysis. In the uni variate analysis patients without nodal metastatic involvement (P = 0.02), less advanced tumour stage (P = 0.02) or TNF-alpha and TGF-beta positive ca ncers (P = 0.01 and P = 0.03) showed a favourable prognosis in terms of ove rall survival. Since our previous studies demonstrated a significant associ ation between NSCLC behaviour, neoangiogenesis and bcl-2 expression, we inv estigated the putative relation between TNF-alpha and TGF-beta on the one h and, and vascular count las a measure of tumour angiogenesis) and bcl-2 pro tein expression, on the other hand. Our results showed a significant direct association between TNF-alpha and bcl-2 (P = 0.05) and an inverse associat ion between TNF-alpha and microvessel count (P = 0.03). Moreover, as previo usly demonstrated, we observed a significant inverse correlation between bc l-2 protein expression and vascular count (P = 0.05), suggesting that the f avourable effect of TNF-alpha on clinical outcome may be related to a bcl-2 -mediated low neovascular development. (C) 2000 Cancer Research Campaign.