Abstract
Abstract Background: Tumor necrosis factor alpha induced protein 8 (TNFAIP8) is a transcription factor NF-kB inducible antiapoptotic and oncogenic molecule. This gene was initially discovered by comparison of expression profiles of primary and metastatic head and neck squamous cell carcinoma (hence earlier referred to as SCC-S2). Positive correlation between TNFAIP8 expression and cancer progression/poor prognosis has been suggested in a few human solid cancers including pancreatic and esophageal primaries. We were the first to publish the adverse prognostic implication of TNFAIP8 expression in prostatic adenocarcinomas. In this study, we evaluated the significance of this protein in normal, inflamed and neoplastic pancreatic tissues. Design: A total of 184 formalin-fixed, paraffin-embedded pancreatic tissues were analyzed; 151 samples in tissue microarray format [79 primary ductal carcinomas (PDC), 5 ductal adenocarcinomas from distant metastatic sites not matched to primary tumors (MDAC), 9 islet cell tumors (ICT) (one carcinoma), 2 chronic pancreatitis (CP), 29 normal adjacent to cancer, 8 normal adjacent to inflammation, and 19 normal pancreatic tissues] and 19 primary tumor resections [19 primary ductal adenocarcinomas (PDAC), 14 of these with normal tissue adjacent to the cancer]. All samples 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 clinicopathologic variables. Results: Immunoreactivity for TNFAIP8 was predominantly cytoplasmic. TNFAIP8 protein overexpression was noted in 44/184 (24%) samples and correlated with tumor type [9/98 (9%) PDC/PDAC 2/5 (40%) unmatched distant MDAC, 5/9 (56%) (ICT) (1/1 carcinoma), 1/2 (50%) (CP), 15/43 (35%) normal adjacent to cancer, 5/8 (63%) normal adjacent to inflammation, and 7/19 (37%) normal pancreatic tissues, p<0.0001], with advanced tumor stage within PDC/PDAC [0/24 (0%) Stage I vs 3/44 (7%) Stage II vs 6/23 (26%) Stage III vs 0/7 (0%) Stage IV, p=0.010], and overall with gender [34/107 (32%) male vs 10/77 (13%) female, p=0.003]. Islets were present in 63 cases, all (100%) showing TNFAIP8 protein overexpression. Conclusion: TNFAIP8 immunohistochemical expression correlates with endocrine phenotype and portends poor prognosis in pancreatic ductal carcinomas. This protein may represent both a novel pathway in endocrine differentiation and a therapeutic target in the management of aggressive PDC, warranting further study. Citation Format: Jeffrey S. Ross, Bhaskar VS Kallakury, Hwa Jeong Lee, David M. Jones, Sanaz Ainechi, Gregory M. Sheehan, Christine E. Sheehan, Usha N. Kasid. TNFAIP8 protein expression in normal, inflammatory and neoplastic pancreatic tissues: Correlation with endocrine phenotype and advanced stage in ductal adenocarcinomas. [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 3836. doi:10.1158/1538-7445.AM2014-3836
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