p16 Expression in Squamous and Trophoblastic Lesions of the Upper Female Genital Tract

p16, a surrogate marker for human papillomavirus (HPV) infection, is uniformly present in HPV-related carcinomas. This study aims to further characterize p16 expression in trophoblastic lesions and squamous lesions of the upper female genital tract, as little data exists. p16 immunostaining was performed on sections from ichthyosis uteri (1), primary uterine corpus squamous cell carcinoma (UCSCC) (2), primary ovarian SCC (OSCC) (5; 2 associated with a dermoid cyst), endometrial endometrioid adenocarcinoma with extensive squamous differentiation (EC-SD) (5), ovarian endometrioid adenocarcinoma with extensive squamous differentiation (OC-SD) (4), placental site nodule (5), and placental site trophoblastic tumor (PSTT) (6). We evaluated the percentage of positive cytoplasmic and nuclear staining (focal = <10%, multifocal = 10% to 50%, and diffuse = >50%) and staining intensity (weak, moderate, and strong). HPV-DNA analysis by polymerase chain reaction was performed on 5 OSCC. Ichthyosis uteri, all UCSCC and 1 OSCC (arising in a dermoid) were negative; the other dermoid-associated OSCC showed focal moderate staining, the remaining OSCC displayed strong (100%), diffuse (2), or multifocal (1) p16 positivity. Three of the 5 EC-SD cases showed strong diffuse staining of the squamous component. The glandular component focally showed strong p16 positivity (2), with variably intense focal staining in 3 cases. The squamous component of all OC-SD showed focal moderate staining, with variable staining of the glandular component. Overall, 3 EC-SD had 80% to 90% p16 positivity. Five of the 5 placental site nodules and 4 of the 6 PSTT showed focal weak staining, whereas 2 PSTT were p16 negative. HPV-DNA analysis was negative in 3 of the 5 OSCC, the other 2 cases being technical failures. p16 is expressed in OSCC and in the squamous and glandular components of EC-SD and OC-SD. As p16 is negative in UCSCC, it may help to identify the origin of SCC diffusely involving the corpus and cervix, and suggests different pathogeneses for SCC of the upper female genital tract, likely to be unrelated to HPV infection. In contrast to earlier data, we found weak and focal p16 expression in trophoblastic lesions. Thus, when considering the differential diagnosis of cervical SCC and trophoblastic lesions, only strong diffuse p16 staining should be considered helpful.