StAR and progesterone producing enzymes (30-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage cytochromes P450) in human epithelial ovarian carcinoma: Immunohistochemical and real-time PCR studies
StAR and progesterone producing enzymes (30-hydroxysteroid dehydrogenase and cholesterol side-chain cleavage cytochromes P450) in human epithelial ovarian carcinoma: Immunohistochemical and real-time PCR studies
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DOI：
10.1111/j.1349-7006.2005.00040.x
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发表时间：
2005-04-01
期刊：
影响因子：
5.7
通讯作者：
Sasano, H
中科院分区：
文献类型：
--
作者：
Abd-Elaziz, M;Moriya, T;Sasano, H
类固醇生成急性调节蛋白（StAR）、P450侧链裂解酶（P450scc）和3β-羟基类固醇脱氢酶（3A-HSD）都参与胆固醇的转运和黄体酮的产生。包括黄体酮在内的性类固醇的原位产生被认为在常见上皮性卵巢癌的发病机制和/或发展中发挥重要作用。在这项研究中，StAR、P450scc 和 3 beta-HSD 在 100 例卵巢癌中进行免疫定位，然后将结果与个体患者的临床病理学和预后参数（包括肿瘤细胞中孕酮受体 (PR) 的状态）相关联。通过实时 PCR 分析对 20 例上皮性卵巢癌的免疫组织化学结果进行了进一步表征，其中冷冻组织可供检查。 StAR、P450scc 和 3 beta-HSD 免疫反应性主要在癌细胞的细胞质中检测到。实时 PCR 分析的结果与免疫组织化学研究的结果相关。 StAR、P450scc 和 3 beta-HSD H 评分与 FIFAO 分期、肿瘤残余大小和 Ki67 LI 存在显着的负统计相关性。 StAR H 评分与 PR-B LI 之间存在统计学上显着的正相关性。多变量统计分析表明，瘤内StAR状态、FIGO分期和残留肿瘤大小均是患者临床结果的独立预后因素。 StAR（一种在人上皮性卵巢癌中用于类固醇生成的胆固醇转运蛋白）的存在可能反映了这些肿瘤原位产生黄体酮的能力，这可能影响这些肿瘤的生物学行为，特别是通过黄体酮依赖性抑制肿瘤细胞增殖。
Steroidogenic acute regulatory protein (StAR), P450 side-chain cleavage enzyme (P450scc) and 3 beta-hydroxysteroid dehydrogenase enzyme (3A-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 3 beta-HSD were immuno-localized 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 3 beta-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 3 beta-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 steroidgenesis 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.