Department of Pathomorphology, Wroclaw Medical University, Wroclaw, Poland.
Pathol Oncol Res. 2011 Sep;17(3):511-8. doi: 10.1007/s12253-010-9340-0. Epub 2011 Jan 6.
Estrogen as a potential factor of ovarian carcinogenesis, acts via two nuclear receptors, estrogen receptor alpha (ERα) and estrogen receptor beta (ERβ), but the cellular signal pathways involved are not completely clear so far. In this study we have described the expression of ERα, detected by immunocytochemistry in 11 ovarian carcinoma cell lines and by immunohistochemistry in 43 Federation Internationale des Gyneacologistes et Obstetristes stage III ovarian carcinoma specimens prepared before and after treatment with cisplatin-based schemes. For cisplatin resistance is a major obstacle in the treatment of ovarian carcinoma, analysis of cisplatin sensitivity in 11 ovarian carcinoma cell line was also performed. The strong nuclear ERα expression was only shown in the single A2780P cell line. Expression of ERα in tissue specimens did not reveal any correlations between histopathological parameters (histologic type and grading). We demonstrated a significant association with ERα expression in specimens from primary laparotomies (PL) and cause-specific survival. In the cases terminated by death of the patient, overall immunoreactivity score of ERα expression at PL was significantly lower than in surviving patients. In addition, Kaplan-Meier analysis revealed significantly shorter overall survival time and progression-free time in cases with lower immunoreactivity score of ERα expression at PL. Our findings support the hypothesis that aberrant hormone activity, by way of altered receptor expression, might be an important factor in the malignant transformation of ovarian cancer.
雌激素作为卵巢癌发生的潜在因素,通过两种核受体,即雌激素受体 alpha(ERα)和雌激素受体 beta(ERβ)发挥作用,但迄今为止,涉及的细胞信号通路尚不完全清楚。在这项研究中,我们通过免疫细胞化学在 11 种卵巢癌细胞系中描述了 ERα 的表达,并通过免疫组织化学在 43 例 Federation Internationale des Gyneacologistes et Obstetristes III 期卵巢癌标本中描述了其表达,这些标本在接受顺铂为基础的方案治疗前后均有准备。由于顺铂耐药是卵巢癌治疗的主要障碍,我们还对 11 种卵巢癌细胞系的顺铂敏感性进行了分析。只有在单一的 A2780P 细胞系中才显示出强烈的核 ERα 表达。组织标本中 ERα 的表达与组织学参数(组织类型和分级)之间没有显示出任何相关性。我们在原发剖腹术(PL)和特定原因的生存中证明了与 ERα 表达的显著相关性。在患者死亡的病例中,PL 时 ERα 表达的总免疫反应评分明显低于存活患者。此外,Kaplan-Meier 分析显示,PL 时 ERα 表达的免疫反应评分较低的病例总生存时间和无进展时间明显缩短。我们的发现支持这样一种假设,即异常激素活性通过改变受体表达,可能是卵巢癌恶性转化的一个重要因素。