Abstract 3264: Mesothelin expression in ovarian tumors and serum autoantibodies of the laying hen model is similar to human ovarian cancer

Proceedings: AACR 101st Annual Meeting 2010‐‐ Apr 17‐21, 2010; Washington, DC Background: Mesothelin (MSLN) is a 40kDa cell-surface differentiation antigen that is normally expressed at low levels and is restricted to tissues such as the mesothelial cells lining some body cavities and epithelial cells of kidney, tonsil, trachea, and fallopian tubes. However MSLN is highly expressed in ovarian cancer, mesotheliomas, and to a lesser extent in other cancers such as pancreatic, lung, and stomach. Soluble MSLN is shed into the circulation and is a potential serum biomarker for ovarian cancer. In addition MSLN autoantibodies are detected in the sera of patients whose tumors were positive for MSLN. The laying hen spontaneously develops progressive ovarian tumors. Ovarian adenocarcinoma in the hen bears a striking histological resemblance to human epithelial ovarian cancer. Furthermore, multiple proteins are similarly expressed in hen and human ovarian tumors. In this study, we hypothesized that MSLN expression is increased in hen ovarian tumors compared to normal ovaries, and that similar to human ovarian cancer, there are circulating anti-MSLN antibodies in response to tumors. Materials and Methods: 31 White Leghorn laying hens were used for sample collection. MSLN mRNA expression in hen ovarian tumors (n=21) and normal ovaries (n=10) was analyzed by Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR). MSLN protein expression was evaluated by immunohistochemistry (IHC) and two-dimensional SDS-Polyacrylamide Gel Electrophoresis (2D-SDS-PAGE) Western blot. Circulating anti-MSLN autoantibodies were assessed by immunoassay of sera from hens with normal ovaries (n=10) and with ovarian tumors (n=10). Results: RT-PCR showed 57% (12/21) of ovarian cancers expressed MSLN. MSLN expression was observed in 3/4 (75%) serous carcinomas, 2/6 (33%) mucinous carcinomas, 1/4 (25%) endometrioid tumors and 6/7 (86%) mixed histology tumors. By tumor stage, 5/8 (62.5%) early stage (I/II) and 7/13 (53.8%) late stage (III/IV) tumors had MSLN expression. None of the normal ovaries had detectable levels of MSLN mRNA. A significant difference of MSLN mRNA expression was seen between tumor and normal (P 0.05). By IHC and 2D Western blot, immunoreactive MSLN protein was detected in tumors with detectable MSLN mRNA, but not in normal ovaries and tumors without detectable MSLN mRNA. Circulating anti-MSLN antibodies occurred in 60% (6/10) of hens with ovarian tumors. Conclusion: MSLN gene and protein expression is elevated in chicken ovarian tumors and not detectable in normal ovaries. The results support the utility of the hen model for preclinical studies of MSLN as a biomarker and target of therapy. Supported by DOD OC073325 (JL) and NIH R01CA134487 (IH & JL). Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 3264.