Status and significance of CpG island methylator phenotype in endometrial cancer

Background: Endometrial cancer is a common gynecologic malignant disease, but patients with advanced disease have a poor prognosis. The CpG island methylator phenotype (CIMP) involves hypermethylation targeted toward the promoters of multiple genes.

Objective: To investigate the role of epigenetic aberration of tumor-related genes in endometrial cancer.

Methods: The promoter methylation status of 5 genes was examined in 35 endometrial cancer tissues, 15 matched adjacent normal endometrial tissues (NET) from the same cancer patients, and 22 benign endometria from unaffected patients by methylation-specific PCR. CIMP positivity (CIMP+) was defined as concordant methylation of ≥3 genes.

Results: The methylation frequency of promoters for the 5 genes in the cancer tissues ranged from 37% for P16 to 57% for P14. Cancer and benign endometria, but not cancer and adjacent NET, significantly differed in methylation of P14, P16, ER, COX-2 and RASSF1A (p < 0.05). CIMP+ was frequent in cancer and adjacent NET (46 and 47%, respectively; p > 0.05), but absent in benign endometria. Moreover, CIMP+ was significantly correlated with methylation of P16 and COX-2 (r = 0.673 and 0.662, respectively; p < 0.001).

Conclusion: CIMP+ is an important and frequent epigenetic event in endometrial cancer or adjacent NET, and may be a biomarker for predicting early carcinogenesis. COX-2 is a good representative gene of CIMP+ in this cancer.