Abstract
Abstract Background: Tumor necrosis factor alpha induced protein 8 (TNFAIP8) is a transcription factor NF-kB inducible antiapoptotic and oncogenic molecule. Positive correlation between TNFAIP8 expression and cancer progression/poor prognosis has been described in a few human solid cancers including pancreatic and esophageal primaries. We were the first to publish the correlation of TNFAIP8 expression with high tumor grade and its independent predictor status for disease recurrence in prostatic adenocarcinomas. In this study, we evaluated the significance of this protein in non small cell lung cancer (NSCLC). Design: A total of 144 formalin-fixed, paraffin-embedded NSCLCs were analyzed (122 primary tumor resections and 22 tissue microarray samples); including 47 squamous cell carcinomas (SCC), 59 adenocarcinomas (AC), and 38 bronchioloalveolar carcinomas (BAC), were immunostained by a manual method using a custom made anti-TNFAIP8 antibody as described earlier (Zhang et al., Int J Cancer,133: 31-42, 2013). The staining pattern was semiquantitatively assessed based on staining intensity and distribution and the results were correlated with morphologic and prognostic variables. Results: Immunoreactivity for TNFAIP8 was predominantly cytoplasmic. TNFAIP8 protein overexpression was noted in 84/144 (58%) tumors and correlated with tumor type [45/59 (76)% AC vs 29/47 (62%) SCC vs 10/38 (26%) BAC, p<0.0001], overall with advanced tumor stage [24/31 (77%) advanced vs 60/113 (53%) early, p=0.015] and lymph node positive status [31/41 (76%) LN+ vs 53/103 (52%) LN-, p=0.008]. Within the AC subgroup, there was a trend toward correlation with advanced tumor stage [13/14 (93%) advanced vs 32/45 (71%) early, p=0.095] and lymph node positive status [18/20 (90%) LN+ vs 27/39 (69%) LN-, p=0.076]. On multivariate analysis, LN+ status independently predicted shortened survival. Conclusion: TNFAIP8 immunohistochemical expression portends poor prognosis in NSCLC and may constitute a novel therapeutic target in the management of aggressive NSCLC, warranting further study. Citation Format: Bhaskar VS Kallakury, Usha N. Kasid, Olga Voronel, Christopher B. Sheehan, Christine E. Sheehan, Jeffrey S. Ross. Adverse prognostic significance of TNFAIP8 protein expression in non small cell lung cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4724. doi:10.1158/1538-7445.AM2014-4724
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