Loss of ARID1A Expression Correlates with Stages of Tumor Progression in Uterine Endometrioid Carcinoma
Tsui-Lien Mao, Laura Ardighieri, Rose Li, Ming-Chieh Lin, Ayse Ayhan, Robert J Kurman, Ie-Ming Shih. Johns Hopkins Medical Institutions, Baltimore; National Taiwan University College of Medicine, Taipei, Taiwan; Seirei Mikatahara General Hospital, Hamamatsu, Japan
Background: ARID1A is a recently identified tumor suppressor which participates in chromatin remodeling that is required to regulate a variety of nuclear activities including gene expression. We previously reported inactivating mutations in 40% and loss of expression of ARID1A in 26% of low-grade uterine endometrioid (FIGO 1) carcinomas.
Design: A total of 70 cases of endometrial lesions were studied for the immunostaining pattern of ARID1A. They included 36 complex atypical hyperplasia (CAH) and 34 high-grade endometrioid (FIGO 2 and 3) carcinomas. Among the 34 high-grade endometrioid carcinomas, there were 8 cases that contained concurrent components of low-grade (FIGO 1) carcinoma. An antibody that was specific for the ARID1A encoded protein was used for immunohistochemistry. Complete loss was defined as absence of ARID1A immunoreactivity in all tumor cells whereas clonal loss was lack of the staining in a discrete tumor area(s) in the background of ARID1A positive tumor cells.
Results: We found that 5 (14%) of 36 cases of CAH displayed clonal loss of ARID1A, but none showed complete loss of ARID1A expression. In contrast, complete and clonal ARID1A loss was detected in 13 (38%) and 2 (6%) of 34 high-grade endometrioid (FIGO 2 and 3) carcinomas, respectively. Among them, 8 cases had concurrent components of low-grade carcinoma. In the low-grade areas from those 8 mixed cases, complete loss of ARID1A was recorded in 2 (25%) and clonal loss in 5 (62.5%) of cases. In three of those 8 cases, ARID1A retention or clonal loss was observed in the low-grade component while complete loss was detected in the adjacent high-grade area.
Conclusions: In summary, clonal loss of ARID1A was found in 14% of CAH but complete loss in 0%. In contrast, complete loss of ARID1A expression was found in approximately 25% of low-grade carcinomas and 38% of high grade carcinomas. These findings strongly suggest that loss of ARID1A staining (presumably due to a mutation) plays an important role in tumor progression in endometrioid carcinoma which may have significant implications to further understand the pathogenesis of uterine endometrioid carcinoma.
Category: Gynecologic & Obstetrics
Wednesday, March 21, 2012 9:30 AM
Poster Session V # 146, Wednesday Morning