Estrogen Receptor Alpha Expression in Ovarian Cancer Predicts Longer Overall Survival

Abstract

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.

MiR-26a Promotes Ovarian Cancer Proliferation and Tumorigenesis

“…Previous study showed that it did not reveal any correlations with histologic type of tumors and ovarian cancer grading [30]. Univariate survival analysis revealed that patients with positive-ERα status had a significant better progression-free survival compared with the patients with no expression[31]. In our results, the expression of miR-26a in specimens and plasma in EOC were much higher than those in normal ovary samples, and miR-26a promote EOC cell proliferation by targeting ERα.…”

Endogenous androgens and risk of epithelial invasive ovarian cancer by tumor characteristics in the European Prospective Investigation into Cancer and Nutrition

“…Given its affinity for the ER, one might speculate that androstendione affects EOC risk via these receptors. The expression of ER in general 38 and especially ERa has been associated with longer overall survival in ovarian cancer patients, 39 whereas the expression of ERb2 in advanced serous ovarian cancer has been associated with an unfavorable prognosis. 40 A recently published pooled analysis on the role of hormone receptors in ovarian cancer survival 38 evaluating tumors by histologic subtype showed no association between ER expression and survival in mucinous or low-grade serous carcinomas, both type I by definition.…”

“…An incidence density sampling protocol was used, such that controls could include subjects who became a case later in time and each control could be sampled more than once. Cases and controls in both study phases were matched on: study recruitment center, age at blood donation (66 months), time of the day of blood collection (61 h), fasting status (<3 h, 3-6 h, >6 h), and menopausal status at blood collection (premenopausal, perimenopausal, postmenopausal), as well as menstrual cycle phase for premenopausal women ("early follicular" (days 0-7 of the cycle), "late follicular" (days 8-11), "peri-ovulatory" (days 12-16), "mid-luteal" (days [20][21][22][23][24], and "other luteal" (days 17-19 or days [25][26][27][28][29][30][31][32][33][34][35][36][37][38][39][40]. Cases missing data on phase of menstrual cycle were matched to controls with missing information on menstrual cycle phase.…”

Steroid Hormones and Ovarian Cancer

“…They determined that patients with higher initial ER expression (>30% of cells) enjoyed longer OS and progression-free survival (PFS) (p=0.0016, p=0.032, respectively). Similarly, Halon et al (2011a) looked at ER expression in the same group of patients and found that loss of ER expression predicted significantly shorter OS and PFS. Another group (Yue et al, 2010) also examined steroid receptors as possible prognostic markers in EOC.…”