title: P16INK4a expression in undifferentiated carcinoma of the uterus does not exclude its endometrial origin.
abstract: Undifferentiated carcinoma of the endometrium is a rare neoplasm, which, when involving the cervix, raises a question about its origin. Diffuse p16 positivity of uterine cancers is usually interpreted as a surrogate marker for high-risk human papilloma virus and favors cervical origin. In this study, we investigated the expression of cytokeratin 7 (CK7), monoclonal carcinoembryonic antigen (mCEA), estrogen receptor (ER), vimentin, and p16 in 28 cases of undifferentiated endometrial carcinoma, 20 high-grade endometrioid adenocarcinomas, and 50 cervical adenocarcinomas. Staining was considered positive when it was cytoplasmic for CK7, mCEA, and vimentin, nuclear for ER, and both nuclear and cytoplasmic for p16. Percentages of cells staining were recorded as follows: negative (0%-5%), 1+ (6%-25%), 2+ (26%-50%), 3+ (51%-75%), and 4+ (>75%). P16 was considered positive if it stained more than 75% of the tumor cells. Diffuse/strongly positive staining for p16 was seen in 40/50 (80%) cases of cervical adenocarcinoma and 14/28 (50%) cases of undifferentiated endometrial carcinoma. In high-grade endometrioid adenocarcinoma, staining was mainly patchy. CK7, mCEA, ER, progesterone receptor, and vimentin staining in undifferentiated endometrial carcinoma was as follows: 10/28 (36%), 4/28 (14%), 21/28 (75%), 23/28 (82%), and 26/28 (93%), respectively; for high-grade endometrioid carcinoma: 20/20 (100%), 1/20 (5%), 17/20 (85%), 18/20 (90%), and 19/20 (95%); for endocervical adenocarcinoma: 50/50 (100%), 45/50 (90%), 9/50 (18%), 8/50 (16%), and 6/50 (12%), respectively. Our data indicate that p16 may play a role in the tumorigenesis of a subset of undifferentiated endometrial carcinoma. In the setting of p16 positivity, undifferentiated endometrial carcinomas are more likely to be ER, progesterone receptor, and vimentin positive and mCEA negative when compared with endocervical adenocarcinomas. Distinction between undifferentiated endometrial carcinoma and endocervical adenocarcinoma, both of which can share diffuse p16 expression, should rely on detection of human papilloma virus in the latter.
authors: Department of Pathology, Sunnybrook Health Sciences Center, University of Toronto, ON, Canada. reda.saad@sunnybrook.ca
authors: Reda S
authors: RS
authors: Saad
authors: Miral
authors: M
authors: Mashhour
authors: Sharon
authors: S
authors: Noftech-Mozes
authors: Nadia
authors: N
authors: Ismiil
authors: Valérie
authors: V
authors: Dubé
authors: Zeina
authors: Z
authors: Ghorab
authors: Hala
authors: H
authors: Faragalla
authors: Mahmoud A
authors: MA
authors: Khalifa
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor / Q000032:analysis / Q000378:metabolism; D002277:Carcinoma / Q000175:diagnosis* / Q000378:metabolism; D018269:Carcinoma, Endometrioid / Q000175:diagnosis* / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000378:metabolism*; D003937:Diagnosis, Differential; D016889:Endometrial Neoplasms / Q000175:diagnosis* / Q000378:metabolism; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D027383:Papillomaviridae / Q000502:physiology; D030361:Papillomavirus Infections / Q000473:pathology / Q000821:virology; D002583:Uterine Cervical Neoplasms / Q000175:diagnosis* / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D014408:Biomarkers, Tumor; D019941:Cyclin-Dependent Kinase Inhibitor p16