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
L. Boldrini et al., 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, BR J CANC, 83(4), 2000, pp. 480-486
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.