WBC DNA methylation was analysed by bisulphite pyrosequencing at ataxia telangiectasia mutated (ATM), estrogen receptor 1 (ESR1), progesterone receptor (PGR), mutL homologue 1 (MLH1), breast cancer susceptibility gene (BRCA1), secreted frizzled-related protein 1 (SFRP1), stratifin (SFN), retinoic acid receptor beta (RARB) loci and the repetitive element LINE1 in 880 SCOTROC1 trial patients [paclitaxel (Taxol)-carboplatin versus docetaxel (Taxotere)-carboplatin as primary chemotherapy for stage Ic-IV epithelial ovarian cancer].
There was significant enrichment of ESR1 binding present in multiple datasets near genomic regions associated with breast cancer (7.45-fold, p = 0.001), height (2.45-fold, p = 0.002), multiple sclerosis (5.97-fold, p < 0.0002) and prostate cancer (4.47-fold, p = 0.0008), and suggestive evidence of ESR1 enrichment for regions associated with coronary artery disease, ovarian cancer, Parkinson's disease, polycystic ovarian syndrome and testicular cancer.
No distinct subgroups of EOC could be identified by unsupervised clustering, however, analyses based on genes correlated with periostin (POSTN) and estrogen receptor-alpha (ESR1) yielded distinct subgroups.
Previous studies have shown that ESR1 methylation influences ovarian cancer development and might thus play a role regarding prognosis of ovarian carcinoma.
Accordingly, immunohistochemical analysis of ERα-negative tissue specimens from HGSOC patients showed a significantly greater TAM infiltration in premenopausal compared to postmenopausal women.
Conversely, estrogen receptor signaling downregulates miR-486-5p and upregulates OLFM4 expression, slowing the development and progression of ovarian cancer.
Expert commentary: The efficacy of endocrine therapy in epithelial ovarian cancer is likely to be confined to histological subtypes with the highest ER expression while low grade serous ovarian cancer appears to be one subgroup with good sensitivity to these agents.
Levels of phosphorylated estrogen receptor alpha (pERα) were evaluated in well, moderate and poorly differentiated EOC samples (EOC-I, EOC-II, EOC-III).
Expression of ER (Hazard Ratio (HR) = 0.18, 95% confidence interval 0.08-0.42, <i>p</i> = 0.0002) and of PR (HR = 0.22, 95% confidence interval 0.10-0.53, <i>p</i> = 0.0011) were significantly associated with longer ovarian cancer specific survival adjusted for age, grade, treatment center, stage, and residual disease.
We constructed polygenic risk scores (PRS) using BC and OC susceptibility SNPs identified through population-based GWAS: for BC (overall, estrogen receptor [ER]-positive, and ER-negative) and for OC.
When considered as continuous variables, ER and AR showed greater expression in primary tumors in comparison with brain metastases (p=0.013 and p=0.032, respectively).In our series, AR predicts brain involvement, with a 9.5 times higher propensity for AR-negative EOC.
Therefore, the present study determined the levels of SULT1E1, STS and estrogen receptor α (ERα) protein in paraffin-embedded specimens from 206 patients with Federation of Gynecology and Obstetrics stage II-IV EOC treated with debulking surgery and standard platinum-based adjuvant chemotherapy.
The majority of serous carcinomas of borderline epithelial ovarian cancerwere ER or PR positive, but in contrast less than 33% of mucinous carcinomas of borderline epithelial ovarian cancerswere ERor PR positive.Furthermore, there was no association between the ER or PR positivity and menopausal status in both malignant and borderline epithelial ovarian cancer.
This study uses primary cultures of mouse ovarian surface epithelium (OSE) to demonstrate that one possible mechanism by which estrogen accelerates the initiation of ovarian cancer is by up-regulation of microRNA-378 via the ESR1 pathway to result in the down-regulation of a tumour suppressor called Disabled-2 (Dab2).