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Status and Significance of CpG Island Methylator Phenotype in Endometrial Cancer

2011; Karger Publishers; Volume: 72; Issue: 3 Linguagem: Inglês

10.1159/000324496

1423-002X

Qingying Zhang, Deqing Yi, Li Zhou, Dong-Hong Zhang, Taimei Zhou,

Cancer-related gene regulation

<i>Background:</i> 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. <i>Objective:</i> To investigate the role of epigenetic aberration of tumor-related genes in endometrial cancer. <i>Methods:</i> 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. <i>Results:</i> The methylation frequency of promoters for the 5 genes in the cancer tissues ranged from 37% for <i>P16</i> to 57% for <i>P14</i>. Cancer and benign endometria, but not cancer and adjacent NET, significantly differed in methylation of <i>P14</i>, <i>P16</i>, <i>ER</i>, <i>COX-2</i> and <i>RASSF1A</i> (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 <i>P16</i> and <i>COX-2</i> (r = 0.673 and 0.662, respectively; p < 0.001). <i>Conclusion:</i> CIMP+ is an important and frequent epigenetic event in endometrial cancer or adjacent NET, and may be a biomarker for predicting early carcinogenesis. <i>COX-2</i> is a good representative gene of CIMP+ in this cancer.