No metastatic cervical adenocarcinomas in a series of p16INK4a-positive mucinous or Endometrioid advanced ovarian carcinomas:: An analysis of the AGO ovarian cancer study group

Epithelial ovarian cancers may represent secondary manifestations of occult extraovarian carcinomas. Such tumors may be misdiagnosed as primary ovarian carcinomas clinically and pathologically. In a recent study, several cases of cervical cancer metastases with primary manifestation as mucinous or endometrioid ovarian carcinomas were described. In all cases, human papillomavirus (HPV) DNA and diffuse p16(INK4a) immunostaining were detected in the ovarian tumor tissues. To estimate the frequency of occult metastatic endocervical adenocarcinomas in a series of mucinous or endometrioid ovarian carcinomas, 24 ovarian cancers with mucinous and 50 with endometrioid differentiation from the Arbeitsgemeinschaft Gynaekologische Onkologie OVAR-3 database were analyzed for HPV and p16(INK4a) positivity. The p16(INK4a) immunostaining was performed using the p16(IN4a) histology kit (Dako, Glostrup, Denmark), and both nuclear and cytoplasmic staining results were considered positive. Human papillomavirus polymerase chain reaction analysis was performed using 2 consensus primer systems (GP5(+)/GP6(+) and PGMY09/11) and HPV-16- and HPV-18-specific primers from the L1 and the E6 regions. Six (8%) of 74 tumors were p16(INK4a)-negative, 13 (18%) of 74 showed single positive cells, 28 (38%) of 74 showed focal homogeneous staining, and 27 (36%) of 74 showed complete diffuse staining. In several independent amplifications of different regions of the HPV genome, none of the 73 tumors available for analysis showed the presence of HPV DNA. No ovarian metastases of endocervical adenocarcinomas were found among mucinous and endometrioid adenocarcinomas from a large chemotherapy trial of advanced stage ovarian carcinomas. The p16(INK4a) staining detected in many primary ovarian adenocarcinomas in the present series seems independent from HPV oncogene activity.