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Tumour necrosis factor-alpha expression in tumour islets confers a survival advantage in non-small cell lung cancer

By Chandra M. Ohri, Aarti Shikotra, Ruth H. Green, David A. Waller and Peter Bradding

Abstract

Background: The role of TNFα in cancer is complex with both pro-tumourigenic and anti-tumourigenic roles proposed. We hypothesised that anatomical microlocalisation is critical for its function.\ud Methods: This study used immunohistochemistry to investigate the expression of TNFα in the tumour islets and stroma with respect to survival in 133 patients with surgically resected NSCLC.\ud Results: TNFα expression was increased in the tumour islets of patients with above median survival (AMS) compared to those with below median survival (BMS)(p = 0.006), but similar in the stroma of both groups. Increasing tumour islet TNFα density was a favorable independent prognostic indicator (p = 0.048) while stromal TNFα density was an independent predictor of reduced survival (p = 0.007). Patients with high TNFα expression (upper tertile) had a significantly higher 5-year survival compared to patients in the lower tertile (43% versus 22%, p = 0.01). In patients with AMS, 100% of TNFα[superscript +] cells were macrophages and mast cells, compared to only 28% in the islets and 50% in the stroma\ud of BMS patients (p < 0.001).\ud Conclusions: The expression of TNFα in the tumour islets of patients with NSCLC is associated with improved survival suggesting a role in the host anti-tumour immunological response. The expression of TNFα by macrophages and mast cells is critical for this relationship.Peer-reviewedPublisher Versio

Publisher: BioMed Central Ltd
Year: 2010
DOI identifier: 10.1186/1471-2407-10-323
OAI identifier: oai:lra.le.ac.uk:2381/8804
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