Prognostic significance of tumor necrosis factors and their receptors in nonsmall cell lung carcinoma

Tran, Tien‐Anh; Kallakury, Bhaskar; Ambros, Robert A.; Ross, Jeffrey S.

doi:10.1002/(sici)1097-0142(19980715)83:2<276::aid-cncr11>3.3.co;2-5

Cited by 9 publications

(18 citation statements)

References 20 publications

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“…In the current study, coexpression of TNF-α, TNFR-I and TNFR-II in NSCLC has been found by RT-PCR assay, as also reported by Tran et al (1998) who used an immunohistochemical technique. The PCR method cannot discriminate between free TNF-α and receptorbound TNF-α, so that the positive signal we found in our cases can either depend on TNF-α secreted by the tumour-infiltrating inflammatory cells, or result from autocrine production by the tumour cells.…”

Section: Tnf-α Expressionsupporting

confidence: 84%

“…In a number of immunohistochemical studies TNF-α has appeared in particular in the cytoplasm of inflammatory cells and tumour-associated macrophages (Pusztai et al, 1994), although a proportion of neoplastic cells have shown to be TNF-α positive in some human cancers such as breast (Leek et al, 1998) and lung carcinomas (Tran et al, 1998). Substantially different results have been obtained in these human models: in breast carcinoma a significant association has been found between TNF-α and thymidine phosphorylase expression, which is a factor known to promote tumour angiogenesis (Fajardo et al, 1992;Fox et al, 1996); in lung cancer, where neoangiogenesis seems to play an unfavourable prognostic role, TNF-α expression has shown to produce a better clinical outcome (Tran et al, 1998). In contrast, an antiproliferative effect of TNF-α has been demonstrated in various malignancies such as prostate (Sherwood et al, 1990), colon (Kemeny et al, 1990), (Heim et al, 1990), (Schiller et al, 1990), kidney carcinomas (Skillings et al, 1992), as well as malignant melanoma (Lienard et al, 1992).…”

Section: Tnf-α Expressionmentioning

confidence: 99%

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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

et al. 2000

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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

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Section: Tnf-α Expressionsupporting

confidence: 84%

Section: Tnf-α Expressionmentioning

confidence: 99%

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

et al. 2000

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“…Reduced expression of this family of proteins in adenocarcinoma may contribute to the invasive properties of this cancer. Moreover, several members of the tumor necrosis factor (TNF) family of proteins and their receptors have demonstrated increased expression in various cancers including NSCLC (49). Our statistical analysis of the SAGE data revealed that expression of the TNF receptor superfamily member 18 gene was increased in squamous cell tumors in addition to the detoxification and antioxidation genes.…”

Section: Hierarchical Clustering Of Tumor and Normal Lung Tissues Basmentioning

confidence: 86%

Molecular characteristics of non-small cell lung cancer

Nacht¹,

Dracheva²,

Gao³

et al. 2001

Proc. Natl. Acad. Sci. U.S.A.

112

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We used hierarchical clustering to examine gene expression profiles generated by serial analysis of gene expression (SAGE) in a total of nine normal lung epithelial cells and non-small cell lung cancers. Separation of normal and tumor, as well as histopathological subtypes, was evident by using the 3,921 most abundant transcript tags. This distinction remained when only 115 highly differentially expressed tags were used. Furthermore, these 115 transcript tags clustered into groups suggestive of the unique biological and pathological features of the different tissues examined. Adenocarcinomas were characterized by high-level expression of small airway-associated or immunologically related proteins, whereas squamous cell carcinomas overexpressed genes involved in cellular detoxification or antioxidation. The messages of two p53-regulated genes, p21 WAF1/CIP1 and 14-3-3, were consistently underexpressed in the adenocarcinomas, suggesting that the p53 pathway itself might be compromised in this cancer type. Gene expression patterns observed by SAGE were consistent with results obtained by quantitative real-time PCR or cDNA array analyses by using a total of 43 lung tumor and normal samples. Thus, although derived from only a few tissue libraries, gene expression profiles obtained by using SAGE most likely represent an unbiased yet distinctive molecular signature for the most common forms of human lung cancer.

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“…Markers previously shown to be associated with improved survival in NSCLC include HLA-DR [19], iNOS [20], MRP 8/14 [21] and TNF-b but not TNF-a [22]. It has also been suggested that reduced TNF-a expression by peripheral blood macrophages, in lung cancer, results in cancer progression [23].…”

mentioning

confidence: 99%

Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival

Ohri¹,

Shikotra²,

Green³

et al. 2009

European Respiratory Journal

252

265

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There is a marked survival advantage for patients with nonsmall cell lung cancer (NSCLC) expressing high numbers of macrophages in their tumour islets. The primary aim of the present study was to determine the immunological phenotype of NSCLC-associated macrophages.CD68 + macrophages expressing markers of a cytotoxic M1 phenotype or a noncytotoxic M2phenotype were identified in the islets and stroma of surgically resected tumours from 20 patients with extended survival (median 92.7 months) and 20 with poor survival (median 7.7 months), using immunohistochemistry. The islet density of both M1 and M2 macrophages was markedly increased in extended compared with poor survival patients. In the extended survival group, M1 islet density was significantly increased compared with M2 density, 70% of islet macrophages were positive for M1 markers versus 38% for M2, and the islet:stromal ratio of M1 macrophages was markedly increased compared with M2. The 5-yr survival for patients with above and below median expression of M1 macrophages in the islets was .75 and ,5%, respectively.Macrophages infiltrating the tumour islets in nonsmall cell lung cancer were predominantly of the M1 phenotype in patients with extended survival. The survival advantage conferred by islet macrophage infiltration may be related to their cytotoxic antitumour activity.

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Prognostic significance of tumor necrosis factors and their receptors in nonsmall cell lung carcinoma

Cited by 9 publications

References 20 publications

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

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

Molecular characteristics of non-small cell lung cancer

Macrophages within NSCLC tumour islets are predominantly of a cytotoxic M1 phenotype associated with extended survival

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