Immunolocalization of Nuclear Transcription Factors, DAX-1 and Ad4BP/SF-1, in Human Common Epithelial Ovarian Tumors: Correlations With StAR and Steroidogenic Enzymes in Epithelial Ovarian Carcinoma Manar Abd-Elaziz, M.D., Takuya Moriya, M.D., Ph.D., Jun-ichi Akahira, M.D., Yasuhiro Nakamura, M.D., Takashi Suzuki, M.D., Ph.D., and Hironobu Sasano, M.D., Ph.D. Summary: Intratumoral steroidogenesis is considered to play important roles in the biologic behavior of common epithelial ovarian carcinoma. Recent studies have dem- onstrated the important roles of Ad4BP/SF-1 and DAX-1 in regulation of steroidogen- esis. In this study, we evaluated DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzyme expressions and their correlations in epithelial ovarian carcinomas to evaluate the possible roles of these factors in regulation of intratumoral steroid metabolism and/or production. Immunolocalization of DAX-1, Ad4BP/SF-1, StAR, and steroidogenic enzymes were examined in 90 epithelial ovarian carcinomas. mRNA expression of these proteins was evaluated using real-time polymerase chain reaction (PCR) in 23 cases for further characterization. DAX-1 and Ad4BP/SF-1 immunoreactivity was detected predominately in the nuclei of tumor cells, whereas that of StAR and ste- roidogenic enzymes was present in the cytoplasm. We detected a significant positive correlation between StAR and steroidogenic enzymes immunoreactivity and Ad4BP/SF-1 and statistically inversed correlation with DAX-1. A positive statistical correlation was detected between intratumoral stromal Ad4BP/SF-1 immunoreactivity and clinicopatho- logic parameters of carcinoma patients. Results of real-time PCR analysis were corre- lated with those of immunohistochemical studies. The status of intratumoral DAX-1, Ad4BP/SF-1, and StAR and steroidogenic enzymes in epithelial cells and intratumoral stromal cells of epithelial ovarian carcinoma may contribute in the progression and/or aggressiveness of these tumors. Key Words: DAX-1—SF-1—Steroidogenic enzymes—Steroidogenesis—Immunohistochemistry. Ovarian cancer is associated with the highest mortality rate in developed countries among all gynecological neo- plasms (1). Human common epithelial ovarian carcino- mas comprise 59% of all ovarian tumors and up to 90% of primary ovarian malignancies. Common epithelial ovarian carcinoma is in general considered one of the highly lethal malignancies of women because it is the fourth leading cause of deaths in the United States and is respon- sible for 140,000 annual deaths in women worldwide (2). Sex steroid metabolism has been postulated to play at least some role in the development and behavior of hu- man common epithelial ovarian carcinoma. Several pre- vious studies suggested the presence of some correlations between sex-steroid hormones and the incidence of de- velopment of ovarian carcinoma, because of a decreased incidence with increased parity and protective effects of From the Department of Pathology, Tohoku University School of Medicine and Tohoku University Hospital, Sendai, Japan. Address correspondence and reprint requests to Dr. Manar Abd- Elaziz, Department of Pathology, Tohoku University School of Medicine 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi Prefecture, 980-8575. International Journal of Gynecological Pathology 24:153–163, Lippincott Williams & Wilkins, Baltimore Ó 2005 International Society of Gynecological Pathologists 153 DOI: 10.1097/01.PGP.0000155075.75209.42