Early uterine serous carcinoma: Clonal origin of extrauterine disease

Uterine serous carcinoma (USC) is an uncommon but aggressive type of endome trial carcinoma that is frequently associated with extrauterine disease des pite minimal or no myometrial invasion. The origin of the extrauterine tumo rs in this setting remains controversial. The majority of USCs (90%) and en dometrial intraepithelial carcinomas (78%), the putative precursor of USC, have g53 mutations, suggesting that p53 alterations occur early in the path ogenesis of USC. To determine if the extrauterine tumors associated with mi nimally invasive USC and endometrial intraepithelial carcinoma (EIC) repres ent metastases or multifocal primary tumors, we examined the mutational pat tern of the p53 gene in 3 cases of minimally invasive USC and 1 case of EIC and in the corresponding extrauterine tumors associated with each of the c ases. In all 4 cases, the primary tumors and the associated extrauterine tu mor foci had identical p53 mutations. Our results support the premise that extrauterine serous tumors found in association with EIC or minimally invas ive USC represent a unifocal process and thus are early metastases.