Hypermethylation ofSOX2Promoter in Endometrial Carcinogenesis

Oscar Gee-Wan Wong,Lili Jiang,Zhen Huo,Huijuan Zhang,Michelle Kwan-Yee Siu,Ester Shuk-Ying Wong,Annie Nga-Yin Cheung

doi:10.1155/2010/682504

Abstract

This paper aimed at investigating the expression and methylation profiles of SOX2, a gene coding for the stem cell-related transcription factor SOX2, in endometrial carcinomas. By methylation-specific polymerase chain reaction (MS-PCR), the methylation status of SOX2 promoter region in 72 endometrial carcinomas and 12 normal endometrial samples was examined. Methylated allele was found in 37.5% (27/72) of endometrial carcinomas but only in 8.3% (1/12) of normal endometrial, significantly more frequent in cancers (P = .0472). SOX2 mRNA level was significantly reduced in endometrial carcinoma compared with nonneoplastic endometrium (P = .045). A significant correlation between SOX2 mRNA expression and hypermethylation of SOX2 was found (P = .024). Hypermethylation of SOX2 tended to be more frequently found in type II serous or clear cell adenocarcinoma. SOX2 methylation was also significantly correlated with shorter survival of patients (P = .046). In conclusion, epigenetic mechanisms may play a crucial role on the transcriptional regulation of SOX2 and loss of SOX2 expression may be related to endometrial carcinogenesis.

Highlights

Endometrial cancer is the most common cancer found in the female genital tract worldwide [1]
This paper aimed at investigating the expression and methylation profiles of SOX2, a gene coding for the stem cell-related transcription factor SOX2, in endometrial carcinomas
Formalin-fixed, paraffin-embedded tissues of 57 cases and frozen tissues of 15 cases of endometrial carcinomas were retrieved for methylation study and mRNA expression analysis. 12 cases of normal endometrium were retrieved for methylation study

Summary

Introduction

Endometrial cancer is the most common cancer found in the female genital tract worldwide [1]. Endometrial cancers generally show favorable prognosis, the incidence is on the rising trend in North America, Europe, and Asia [2, 3]. There are two major types of endometrial carcinomas exhibiting different histopathology, cell biology, clinical course, and underling genetic alterations [4]. 70–80% endometrial cancers show endometrioid differentiation and were designated as Type I carcinomas. They are often preceded by premalignant endometrial hyperplasia, which is presumably caused by long-duration unopposed oestrogenic stimulation. Type I carcinomas generally have favorable outcome. Common genetic changes of Type I carcinomas include mutations of K-RAS and PTEN genes, microsatellite instability (MSI) and alteration of beta-catenin [4]. Despite the recent advances in molecular diagnostics, the most important factors in predicting patient prognosis remain to be tumor grade, stage, and subtypes [5, 6]

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