Abstract 1335: Immune regulation in endometriosis and epithelial ovarian cancer

Abstract Objective: Examine the expression and immunogenicity of a known ovarian tumor-associated antigen, MUC1, in ectopic endometriosis lesions and epithelial ovarian cancer (EOC). Determine whether an imbalance in CD4 T cell subsets contributes towards endometriosis pathogenesis and ovarian carcinogenesis. Methods: Biologic specimens were obtained from women with endometriosis, endometriosis-related (endometrioid and clear cell) or serous EOC, and healthy controls, according to University of Pittsburgh IRB protocols. MUC1 and immune cell expression were determined via immunohistochemistry (IHC). Anti-MUC1 IgM and IgG antibody levels were determined via ELISA. Peripheral blood mononuclear cells and cryopreserved cell suspensions from tissue lesions were immunophenotyped using multicolor flow cytometry. Stroma and epithelial cells from tissue biopsies were collected by laser capture microdissection (LCM) and examined with immune-based quantitative RT-PCR arrays. Results: MUC1 was overexpressed in 67% of endometriosis and 89% of EOC lesions. Women with early or late stages of endometriosis had significantly higher anti-MUC1 IgM responses when compared to those women with endometriosis-related EOC (25.3 % of positive control vs.14.2%, p=0.03; 26.3 vs. 14.2%, p=0.04) and to those with serous EOC (25.3 vs. 14.6%, p=0.04; 26.3 vs.14.6%, p=0.04). Women without disease also had significantly higher anti-MUC1 IgM responses compared to endometriosis-related (29.2 vs.14.2%, p=0.01) and serous EOC (29.2 vs.14.6%, p=0.02). Immune cells, including CD3, CD4, and CD8 T cells, are present in endometriotic lesions and appear more abundant than in eutopic endometrium. Flow cytometric analysis of endometriotic lesion-infiltrating T cells revealed a decrease in the frequency of IFN-γ CD4 and CD8 T cells, similar to that seen in patients with EOC. Conclusions: MUC1 is present and appears to be overexpressed in ectopic endometriotic and EOC lesions. Women with endometriosis-related EOC or with serous EOC had significant lower anti-MUC1 IgM levels, suggesting that a compression of antigen-specific humoral (i.e., Th2 driven) immunity may play a role in carcinogenesis. Endometriotic and EOC lesions also appear to have diminished Th1 immunity, suggesting a possible role for local immune suppression. Quantitative analyses of several immune genes in the lesion microenvironment are currently ongoing and will potentially contribute to immune biomarker discovery and improvements in the early detection and prevention of ovarian cancer. 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 1335.