Evidence Supporting Endometriosis as a Precursor of Ovarian Clear Cell and Endometrioid Carcinoma Based on Expression of ARID1A
Ayse Ayhan, Tsui-Lien Mao, Chen-Hsuan Wu, Hiroshi Ogawa, Masayuki Futagami, Hiroki Mizukami, Yoshihito Yokoyama, Robert J Kurman, Ie-Ming Shih. Johns Hopkins Medical Institutions, Baltimore, MD; Seirei Mikatahara Hospital, Hamamatsu, Japan; National Taiwan University College of Medicine and National Taiwan University Hospital, Taipei, Taiwan; Hirosaki University Graduate School of Medicine, Hirosaki, Japan
Background: ARID1A is a recently identified tumor suppressor gene involved in chromatin remodeling. Somatic inactivating mutations and loss of expression of ARID1A are most frequently detected in ovarian clear cell and endometrioid carcinomas and uterine endometrioid carcinomas.
Design: Since endometriosis is thought to be a precursor of ovarian endometrioid and clear cell carcinomas, we undertook an immunohistochemical analysis using an antibody against the ARID1A protein, comparing its expression in ovarian clear cell carcinomas (n=25), well-differentiated endometrioid carcinomas (n=16) and mixed clear cell and endometrioid carcinomas (n=4) and the associated endometriotic cysts (total 45 cases).
Results: ARID1A loss occurred in 30 (67%) of the total 45 ovarian endometriotic cysts with concurrent ovarian carcinomas. In 12 of the 45 cases, ARID1A immunoreactivity was retained in both the endometriotic cyst and the concurrent carcinoma and thus they were not informative. Of the 33 informative cases, there were 21 clear cell carcinomas, 10 endometrioid carcinomas and two mixed clear cell and endometrioid carcinomas. Among these cases ARID1A loss was demonstrated in both the endometriotic cyst and the associated carcinoma in 19/21 (90%) clear cell carcinomas, 9/10 (90%) endometrioid carcinomas and in 2/2 (100%) mixed clear cell and endometrioid carcinomas; in contrast, it was retained in the endometriotic cyst and lost in the carcinoma in the remaining cases. None of the cases demonstrated ARID1A loss in the endometriotic cyst but ARID1A retention in the associated carcinoma. Thus, loss of ARID1A staining occurred in both the endometriotic cyst and the carcinoma in 30 (91%) of 33 informative cases.
Conclusions: Our findings support the role of endometriosis as a precursor of clear cell and endometrioid carcinoma. It appears that loss of ARID1A expression (presumably due to a mutation) is an early molecular event in the development of the majority of ovarian clear cell and endometrioid carcinomas, most occurring before malignant transformation from pre-existing endometriosis and some in the transition from endometriosis to carcinoma.
Category: Gynecologic & Obstetrics
Tuesday, March 20, 2012 1:00 PM
Poster Session IV # 144, Tuesday Afternoon