Alteration of G2 Cell Cycle Regulators Occurs during Carcinogenesis of the Endometrium

OBJECTIVES: In this study, we examined the alteration of the G2 pathway in endometrial hyperplasia (EH) and endometrioid-type endometrial cancer (EC), and analyzed the relationship between the G2 pathway status and the p53 pathway status. METHODS: A total of 103 cases (proliferative phase of the endometrium: 20, EH: 22, and endometrioid-type EC: 61 (I: 39, II: 5, III: 15, recurrence: 2)) were included in this study. We examined the ATM, chk2, CDC25C, cdc2, and cyclin B1 protein expression by immunohistochemistry. In 55 cases (EH: 15; EC: 40), we analyzed CHK2 mutations by RT-PCR-SSCP. RESULTS: There were no CHK2 mutations in endometrial disease. Elevated or reduced expression rates of ATM, chk2, CDC25C, cdc2 and cyclin B1 were 4.5% (1/22), 0%, 0%, 0% and 4.5% (1/22) in EH and 3.3% (2/61), 4.9% (3/61), 13.1% (8/61), 9.8% (6/61) and 9.8% (6/61) in EC. Alteration of the G2 pathway was higher in EC (32.8%; 20/61) than in EH (9.1%; 2/22; p = 0.047). The G2 pathway was significantly higher in the altered p53 pathway group (48.4%; 15/31) than in the normal p53 pathway group (16.7%; 5/30) in EC (p = 0.0134). The altered p53 pathway tended to be related with the cdc2/cyclin B1 status (p = 0.0529). CONCLUSIONS: Alteration of the G2 pathway is thought to occur during carcinogenesis of the endometrium.