De Sousa Damião Robério, Fujiyama Oshima Celina Tizuko, Stávale João Norberto, Gonçalves Wagner José
Discipline of Gynecologic Oncology, Department of Gynecology, Federal University of São Paulo, São Paulo, Brazil.
Oncol Rep. 2007 Jul;18(1):25-32.
Sex hormones are involved in the carcinogenesis of some gynecologic cancers, and the status of their receptors represents an indicator of prognosis and of the therapeutic response in breast and endometrial cancers. In the ovary, this role is not clearly defined, with epithelial cancers being poorly responsive to hormone therapy. COUP-TFI (chicken ovalbumin upstream promoter-transcription factor I) is an orphan nuclear receptor, which is expressed in various tissues and regulates the estrogen receptor (ER) by competition for DNA binding. To investigate the role of these receptors in ovarian carcinogenesis and their implications for cancer prognosis, we evaluated the immunohistochemical expression of ER, progesterone receptor (PR) and COUP-TFI in benign and malignant ovarian epithelial neoplasms and in normal ovaries. A total of 113 ovarian specimens, including 40 diagnosed as malignant epithelial neoplasms (group A), 45 as benign epithelial tumors (group B), and 28 from normal ovaries (group C) were analyzed. Immunoexpression of ER was observed in 70% of patients of group A, 57.8% of group B and 57.1% of group C, with no significant difference between groups (p=0.426). Immunoexpression of PR was significantly lower in group A (12.5%) compared to group B (42.2%) and group C (32.1%) (p=0.010). Similarly, COUP-TFI was expressed in only 10% of group A patients, a rate significantly lower than that observed for group B (31.1%) and group C (39.3%) (p=0.014). No association was observed between the expression of these markers and increased survival or clinical prognostic variables. Multivariate analysis revealed a residual tumor <1 cm as the most significant clinical prognostic factor in group A (p=0.010, OR=4.14). These data support the importance of cytoreduction in the treatment of ovarian cancer, the role of steroid receptors in the mechanism of carcinogenesis, and the need for selection of subgroups that may respond to hormone therapy.
性激素参与某些妇科癌症的致癌过程，其受体状态是乳腺癌和子宫内膜癌预后及治疗反应的一个指标。在卵巢中，这一作用尚未明确界定，上皮性癌对激素治疗反应不佳。COUP-TFI（鸡卵清蛋白上游启动子转录因子I）是一种孤儿核受体，在多种组织中表达，并通过竞争DNA结合来调节雌激素受体（ER）。为了研究这些受体在卵巢癌发生中的作用及其对癌症预后的影响，我们评估了ER、孕激素受体（PR）和COUP-TFI在良性和恶性卵巢上皮性肿瘤以及正常卵巢中的免疫组化表达。共分析了113份卵巢标本，其中40份被诊断为恶性上皮性肿瘤（A组），45份为良性上皮性肿瘤（B组），28份来自正常卵巢（C组）。A组70%的患者、B组57.8%的患者和C组57.1%的患者观察到ER免疫表达，各组之间无显著差异（p=0.426）。与B组（42.2%）和C组（32.1%）相比，A组PR免疫表达显著较低（12.5%）（p=0.010）。同样，COUP-TFI仅在A组10%的患者中表达，该比例显著低于B组（31.1%）和C组（39.3%）（p=0.014）。未观察到这些标志物的表达与生存率增加或临床预后变量之间的关联。多因素分析显示，残留肿瘤<1 cm是A组中最显著的临床预后因素（p=0.010，OR=4.14）。这些数据支持了肿瘤细胞减灭术在卵巢癌治疗中的重要性、类固醇受体在致癌机制中的作用以及选择可能对激素治疗有反应的亚组的必要性。
