SFRP1 promoter methylation and its contribution to endometrial tumorigenesis

B137

Purpose: The secreted frizzled-related protein 1 (SFRP1) encodes a wnt/beta-catenin signalling antagonist and is frequently inactivated by promoter hypermethylation in tumors. We hypothesized that epigenetic inactivation of SFRP1 may be causally involved in the development of endometrial cancer. We undertook a study to examine the contribution of SFRP1 promoter methylation and its association with tumor microsatellite instability (MSI) status among patients with endometrial carcinomas of the endometriod type.
 Methods: Formalin-fixed, paraffin-embedded tissue sections of endometrial adenocarcinomas and matched normal tissue specimens were obtained from patients (n=56) and DNA was extracted from microdissected specimens enriched for tumor and normal cell populations. MSI status was determined using five National Cancer Institute (NCI) consensus panel markers and the methylation status of SFRP1 promoter was analyzed by methylation-specific PCR (MSPCR) assay of sodium bisulfite treated DNA obtained from these specimens. Beta-catenin expression was assessed in a subset of endometrial tumors by immunohistochemistry.
 Results: We found that a majority of tumors (87%) show some degree of SFRP1 promoter methylation at the region examined, however 16% of tumors showed exclusive hypermethylation in tumors. There were 30 MSS and 26 MSI endometrial cancer cases. No significant correlation was observed with either tumor MSI status or with strong nuclear beta-catenin expression.
 Conclusion: Epigenetic inactivation of SFRP1 is a common event in endometrial cancer. It is possible that for a small subset of cases, SFRP1 promoter hypermethylation may play a role in tumorigenesis either through Wnt or an alternative pathway.