Does P16 Expression in Undifferentiated Carcinoma of the Uterus Exclude Its Endometrial Origin?
H Faragalla, MA Khalifa, N Ismiil, S Nofech-Mozes, V Dube, Z Ghorab, RS Saad. Sunnybrook Health Sciences Centre, Toronto, Canada
Background: Undifferentiated carcinoma of the endometrium is a rare neoplasm which, when involving the cervix, raises a question about tumor origin. Immunohistochemistry with p16 antibody plays a role in differentiating cervical from endometrial carcinomas since diffuse p16 positivity can be regarded as a surrogate marker of the presence of high-risk human papillomavirus (HPV) and favors the cervical origin. In this study, we investigated the expression of CK7, ER and p16 in undifferentiated endometrial carcinoma.
Design: Twenty eight cases of undifferentiated endometrial carcinoma were retrieved from the archives of anatomic pathology during the period between January 2000 and December 2007. In addition, 20 cases of high grade endometrial endometrioid adenocarcinoma and fifty cases of endocervical adenocarcinoma were included in the study as control groups. All cases were subjected to total hysterectomy and reviewed to confirm the diagnosis. Cases were stained for CK7, ER and p16. Staining was considered positive when it was cytoplasmic for CK7, nuclear for ER and both nuclear and cytoplasmic for p16. Percentage of cells staining was recorded as follow: Negative (0-5%), weak (1+, 6-25%), moderate (2+, 26-50%) and strong (3+, >50%). P16 was considered as positive if stained more 50% of the tumor cells.
Results: Majority of cervical adenocarcinomas (47/50, 94%) demonstrated diffuse/moderate-strong p16 expression with score 3+ (>50%). In undifferentiated endometrial carcinomas, 16/28 (57%) were strongly positive for p16 (score 3+, >50%). In high grade endometrioid adenocarcinoma, staining was weak or/and focal (score 1+). CK7 was positive in 10/28 (36%) of undifferentiated carcinoma, 20/20 (100%) in endometrioid carcinoma and 50/50 (100%) in endocervical adenocarcinoma. Estrogen receptors were positive in majority of undifferentiated carcinoma 24/28 (86%), all endometrioid carcinoma 20/20 (100%) and in 3/50 (6%) of endocervical carcinoma.
Conclusions: Our data indicate that p16 may play a role in the tumorigenesis of the subset of undifferentiated endometrial carcinoma. In the setting of p16 positivity, undifferentiated endometrial carcinomas are more likely to be ER positive when compared to endocervical adenocarcinomas. Distinction between undifferentiated endometrial carcinoma and endocervical adenocarcinoma, both of which can share diffuse p16 expression, should rely on detection of HPV in the latter.
Category: Gynecologic & Obstetrics
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 152, Monday Morning