DNA methylation status of oestrogen receptor beta(er-b) gene in ovarian cancer

Abstract

Aims: To determine the methylation status of ER-B in ovarian cancer tissue samples and to correlate methylation status with ER-B expression and clinical outcomes. Methods: ER-B methylation status was determined by methylation specific PCR in 155 ovarian cancer tissue samples with known ER-B mRNA expression from previous studies. Methylation status was correlated with ERB expression, histology, FIGO staging, disease free and overall survival, with a median follow up of 80 months. Results: 64 samples showed complete methylation for ERB, 74 samples showed partial methylation and 17 samples were unmethylated. Methylation status did not correlate with age, histology or ER-B mRNA expression. However, complete hypermethylation was significantly associated with late (stage 2-4) disease ( 72.6% vs 41.2%, p=0.016, ? 2 test) and there was significantly more recurrence in women with hypermethylated tumours compared with those with unmethylated tumours ( 36.7% vs 7.1%, p=0.029, ? [2</sup> test ). Women with complete hypermethylated tumours had significantly worse 5 year disease free survival ( 51% vs 86% , p= 0.017 log rank test ) and overall survival ( 43% vs 86% , p=0.033, log rank test ) compared with those with unmethylated tumours. Using Cox regression analysis with age, stage of disease, grade, histology and methylation status as covariates, methylation status remained a significant predictor for disease free and overall survival (p=0.007 and p=0.028 respectively). Conclusion: ER-B methylation status does not reflect ER-B mRNA expression but is a significant predictor for clinical outcomes.