Molecular Identification of “Latent Precancers” for Endometrial Serous Carcinoma in Benign-Appearing Endometrium

Alteration of p53 is an early event in the development of endometrial serous carcinoma (ESC). We have recently identified a group of benign-looking endometria with p53 overexpression, designated “p53 signatures.” In this study, we investigated these p53 signatures and evaluated whether they represented “latent” precancers for ESC. The p53 signatures were specifically associated with ESC, frequently found in the benign-appearing endometrium adjacent to the ESC and only rarely in either the endometrium adjacent to endometrioid carcinomas or in non-cancerous uteri. Forty-two percent of the p53 signature samples showed at least one p53 gene mutation. There were eight ESC uteri with p53 signatures that revealed p53 gene mutations. In four (50%) of these cases, at least one identical p53 gene mutation was found in the signature glands, precancerous regions, and cancerous areas within the same uterus. We concluded that p53 gene mutations apparently precede the morphological changes in affected endometrial cells. The finding of identical p53 mutations in the p53 signatures, precancerous regions, and ESCs in a subset of the uteri provides further evidence of a probable shared lineage between these lesions and suggests that the epithelia that display these p53 signatures are likely latent ESC precancerous regions. These findings underscore the significance of the p53 signature as a target for further research in the early detection and prevention of ESC.