Precursors of Type II Endometrial Cancer

P53 signature - latent precancer of type II endometrial cancer

Based on our previous studies, it is concluded that alteration of p53 occurs not only in well developed ESC, but also in its early form (endometrial intraepithelial carcinoma, EIC) and precancerous form (endometrial glandular dysplasia, EmGD). We have recently identified a group of benign-looking endometria with p53 overexpression, which we designated as “p53 signatures”. Strictly speaking, “p53 signatures” represent those endometrial epithelial cells, with either glandular or surface growth patterns, which are morphologically unremarkable but display diffuse and strong p53 nuclear staining. The following panel contains representative pictures of p53 signatures. The upper left shows surface endometrium is strongly positive for p53 nuclear overexpression, but in the corresponding H&E section (upper right), these p53 positive cells are morphologically unremarkable. Similarly the single p53 positive gland in lower left panel shows no morphologic changes (lower right).

The p53 signatures were specifically associated with ESC, being frequently found in the benign-appearing endometrium adjacent to ESC and only rarely in the endometrium adjacent to endometrioid carcinomas or in non-cancerous uteri. Our recent study showed that 42% of the p53 signature samples showed at least one p53 gene mutation. There were 8 ESC uteri with p53 signatures showing p53 gene mutations. And high concordant p53 mutations present in p53 signatures, EmGD, EIC/ESC within the same uterus. The finding of identical p53 mutations provides further evidence of a probable shared lineage between those lesions, and suggests that the p53 signature epithelia/glands are likely latent precancers