Uterine serous
carcinomas typically have a characteristic morphology (papillary architecture, high-grade nuclei) and immunoprofile (diffuse/strong p53 expression, loss of
hormone receptor expression) that distinguish them from most endometrial
endometrioid carcinomas. However, glandular variants of serous
carcinoma can simulate Fédération Internationale de Gynécologie et d'Obstétrique (FIGO) grade 2
endometrioid carcinomas, and some serous
carcinomas lack p53 expression and retain
hormone receptor expression, making classification difficult. P16 expression patterns distinguish
endometrioid carcinomas (patchy) from human papillomavirus (HPV)-related endocervical
adenocarcinomas (diffuse/strong) but utility for distinction of serous
carcinomas from
endometrioid carcinomas and endocervical
adenocarcinomas has not been evaluated in a large series. Immunohistochemical analysis of p16 expression was performed on 201 uterine and endocervical
adenocarcinomas in
hysterectomy specimens, including 49 serous
carcinomas, 101 endometrial
endometrioid carcinomas (44 FIGO grade 1, 40 FIGO grade 2, and 17 FIGO grade 3), and 51 HPV-related endocervical
adenocarcinomas. All serous
carcinomas demonstrated diffuse/moderate-strong p16 expression, with percentage of positive
tumor cells ranging from 90% to 100% (mean/median: 95%/100%). In contrast, endometrial
endometrioid carcinomas exhibited less diffuse and less intense expression, with percent of positive
tumor cells ranging from 10% to 90% (mean/median: 38%/30%; staining intensity: variable). Similar to serous
carcinomas, all endocervical
adenocarcinomas exhibited diffuse/moderate-strong p16 expression, with percentage of positive
tumor cells ranging from 90% to 100% (mean/median: 94%/90%). P16 can serve as an additional diagnostic marker, used as part of an immunohistochemical panel, including p53 and
hormone receptors, for distinction of uterine serous
carcinomas from
endometrioid carcinomas. Distinction of serous
carcinomas from endocervical
adenocarcinomas (HPV-related type), both of which share diffuse p16 expression and frequently lack
hormone receptor expression, relies on morphology and diffuse/strong p53 expression in the former and detection of HPV in the latter.