Loss of 5-hydroxymethylcytosine (5-hmC) expression in endometrioid type endometrial carcinoma

Objectives: Epigenetic alterations such as DNA methylation are important in cancer development. Recently, the epigenetic marker 5-hydroxymethylcytosine (5-hmC) has been shown to be reduced in a variety of cancers and involved in the process of malignant transformation. The expression of 5-hmC in proliferative endometrium and endometrial carcinoma has not been well elucidated. The aim of this study was to investigate 5-hmC protein expression in proliferative endometrium (PE) and endometrioid type endometrial carcinoma (ETEC). Materials and Methods: The authors examined the expression of 5-hmC by immunohistochemistry in a total of 60 cases comprised of 29 PE and 31 ETEC. The percentage of nuclear staining was estimated for each case as: 0-25%, 26-50%, and > 50% loss. Endometrial stroma was used as a positive control for the 5-hmC staining. Results: Among the 29 PE cases, 28 (97%) had strong and diffuse staining with minimal to no loss of 5-hmC expression (≤ 25% of the cells). A loss of 5-hmC staining was observed in > 25% of the cells in 25 of 31 (81%) ETEC cases, of which 16 (52%) of these cases displayed a loss in > 50% of the tumor cells. The loss of 5-hmC expression was significantly increased in ETEC cases in comparison to the PE cases (p < 0.0001) by Fishers exact test. Conclusions: This study demonstrates that 5-hmC expression is significantly reduced in ETEC compared with PE. These findings suggest that the loss of 5-hmC is an epigenetic event in ETEC and may play a role in its development and progression.

5-hmC; 5-hydroxymethylcytosine; Immunohistochemistry; Endometrium; Endometrial carcinoma

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