Abstract 1497: Aldehyde dehydrogenase 1A1 expression is altered in ovarian cancer and is not associated with stem cells

Abstract

Abstract Ovarian cancer (OvCa) is the leading cause of death from gynecologic malignancies. Tumors with serous histology are the most common and have the poorest prognosis among ovarian cancers. We identified Aldehyde dehydrogenase 1A1 (ALDH1) as an autoantigen in infertility patients, where infertility is an epidemiologic risk factor for OvCa. Aldehyde dehydrogenases belong to a family of detoxifying enzymes that may be related to the aggressiveness of various cancers. In breast and liver cancer, the cytosolic isoform, ALDH1, appears to be associated with cancer stem cells (CSC) and its high expression in breast tumors correlates with poor prognosis. Furthermore, ALDH1 expression is implicated in increased cell proliferation (aggressive behavior) in a lung cancer cell line. In contrast, studies show that ALDH1 is significantly higher in early stages of OvCa and high ALDH1expression is correlated with an increased OvCa patient survival. We hypothesized that ALDH1 expression differs in normal ovary and ovarian tumors and, unlike breast cancer, is not associated with CSCs and an aggressive OvCa phenotype. Methods: We compared ALDH1 with CD133 & CD44 (established CSC markers) mRNA and protein expression using quantitative Real-Time PCR (qPCR) and double label immunohistochemistry (IHC) in human normal ovary and tumors (benign and malignant) with serous histology. The percent of ALDH1 stained cells in at least 3 sections/ ovary were counted using unbiased StereoInvestigator cell counting software. The co-expression of ALDH1 and CD133/CD44 was assessed in malignant tumors by double labeled IHC and flow cytometry. Results: ALDH1 mRNA expression was significantly reduced (p<0.05) in malignant ovarian tumors compared to normal ovaries and benign ovarian tumors. ALDH1 was predominantly expressed in stromal fibroblasts along with surface epithelium in normal ovary. In malignant OvCa, ALDH1 was associated with tumor cells while in benign tumors it was associated with both tumor and normal ovarian stroma. Cells expressing ALDH1 were more numerous in normal ovaries (26.53 ± 2.69%; n=5; p<0.01) and serous benign tumors (22.89 ± 1.78%; n=3; p<0.05) compared to serous carcinomas (13.36 ± 6.23 %; n=5). ALDH1 was rarely co-expressed in CSCs. Conclusions: We compare for the first time, ALDH1 expression and differences in localization in normal and tumor ovaries and lack of ALDH1 co-expression in putative ovarian CSCs. Interestingly, ALDH1 mRNA and protein expression in benign tumors was intermediate between normal ovary and malignant tumors. ALDH1 expression was higher in non-CSCs and was significantly lower in malignant tumors suggesting OvCa differs from breast and liver cancer with regard to ALDH1 expression. Significance: Thus expression of ALDH1 may be advantageous in OvCa and loss of ALDH1 expression might be involved in malignant transformation. Support: NIH R01AI055060, Ovarian Cancer Survivors Network. 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 1497.