StAR and progesterone producing enzymes (3beta-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage cytochromes P450) in human epithelial ovarian carcinoma: immunohistochemical and real-time PCR studies.
Steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc) and 3 beta-hydroxysteroid dehydrogenase enzyme (3beta-HSD) are all involved in the transport of cholesterol and production of progesterone. In situ production of sex steroids including progesterone have been considered to play important roles in pathogenesis and/or development of common epithelial ovarian carcinomas. In this study, StAR, P450scc, and 3beta-HSD were immunolocalized in 100 cases of ovarian carcinoma and results were then correlated with clinicopathological and prognostic parameters of individual patients including status of progesterone receptor (PR) in tumor cells. Results of immunohistochemistry were further characterized by real-time PCR analysis in 20 cases of epithelial ovarian carcinomas in which frozen tissues were available for examination. StAR, P450scc, and 3beta-HSD immunoreactivity was detected predominately in the cytoplasm of carcinoma cells. Results of real-time PCR analysis were correlated with those of immunohistochemical studies. StAR, P450scc, and 3beta-HSD H scores demonstrated significant inversed statistical correlation with FIGO stage, residual size of the tumor, and Ki67 LI. A positive statistically significant correlation was detected between StAR H score and PR-B LI. Multivariate statistical analysis demonstrated that the status of intratumoral StAR, FIGO stage, and residual tumor size all turned out to be independent prognostic factors for the clinical outcome of the patient. The presence of StAR, a cholesterol transporter for steroidogenesis in human epithelial ovarian carcinoma, may reflect the ability of these tumors to produce progesterone in situ that could influence biological behavior of these tumors, especially through progesterone dependent inhibition of tumor cell proliferation.
Abd-Elaziz
Manar
M
Department of Pathology, Tohoku University School of Medicine and Tohoku University Hospital, 2-1 Seiryo-machi, Aoba-ku, Sendai, Miyagi 980-8575, Japan. manarpatholo@yahoo.com
Moriya
Takuya
T
Akahira
Jun-ichi
J
Suzuki
Takashi
T
Sasano
Hironobu
H
D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism*; D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D002277:Carcinoma / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000378:metabolism*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology; D010750:Phosphoproteins / Q000378:metabolism*; D011374:Progesterone / Q000378:metabolism; D011379:Prognosis; D011980:Receptors, Progesterone / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D000098682:Steroidogenic Acute Regulatory Protein
D014408:Biomarkers, Tumor; D010750:Phosphoproteins; D011980:Receptors, Progesterone; D000098682:Steroidogenic Acute Regulatory Protein; D011374:Progesterone; D015067:17-Hydroxysteroid Dehydrogenases; D002786:Cholesterol Side-Chain Cleavage Enzyme