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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 Cancer. 2000 Aug; 83(4):480-6.BJ

Abstract

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-alpha) and transforming growth factor 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 clarified. 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 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-alpha and TGF-beta 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-alpha and TGF-beta 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-alpha and bcl-2 (P = 0.05) and an inverse association between TNF-alpha 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-alpha on clinical outcome may be related to a bcl-2-mediated low neovascular development.

Authors+Show Affiliations

Department of Oncology, University of Pisa, Italy.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

10945495

Citation

Boldrini, L, 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." British Journal of Cancer, vol. 83, no. 4, 2000, pp. 480-6.
Boldrini L, Calcinai A, Samaritani E, 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 Cancer. 2000;83(4):480-6.
Boldrini, L., Calcinai, A., Samaritani, E., Pistolesi, F., Mussi, A., Lucchi, M., Angeletti, C. A., Basolo, F., & Fontanini, G. (2000). 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. British Journal of Cancer, 83(4), 480-6.
Boldrini L, 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 Cancer. 2000;83(4):480-6. PubMed PMID: 10945495.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Boldrini,L, AU - Calcinai,A, AU - Samaritani,E, AU - Pistolesi,F, AU - Mussi,A, AU - Lucchi,M, AU - Angeletti,C A, AU - Basolo,F, AU - Fontanini,G, PY - 2000/8/17/pubmed PY - 2000/8/29/medline PY - 2000/8/17/entrez SP - 480 EP - 6 JF - British journal of cancer JO - Br. J. Cancer VL - 83 IS - 4 N2 - 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-alpha) and transforming growth factor 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 clarified. 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 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-alpha and TGF-beta 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-alpha and TGF-beta 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-alpha and bcl-2 (P = 0.05) and an inverse association between TNF-alpha 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-alpha on clinical outcome may be related to a bcl-2-mediated low neovascular development. SN - 0007-0920 UR - https://www.unboundmedicine.com/medline/citation/10945495/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_ L2 - http://dx.doi.org/10.1054/bjoc.2000.1345 DB - PRIME DP - Unbound Medicine ER -