Clinicopathological Significance of ARID1A Immunoreactivity in Ovarian Clear Cell Carcinoma.
Daichi Maeda, Tsui-Lien Mao, Masashi Fukayama, Tian-Li Wang, Ie-Ming Shih. Graduate School of Medicine, The University of Tokyo, Japan; National Taiwan University Hospital, and College of Medicine, Taipei, Taiwan; Johns Hopkins Medical Institutions, Baltimore, MD
Background: Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A are the most common molecular genetic changes in ovarian clear cell carcinoma (CCC). ARID1A mutations which occurred in approximately half of CCC cases, lead to deletion of the encoded protein and inactivation of the putative tumor suppressor.
Design: In this study, we first correlated ARID1A mutation status and ARID1A immunoreactivity then applied immunohistochemistry to determine if there is any clinicopathological features associated with the loss of ARID1A expression in a total of 149 CCC cases collected from the University of Tokyo Hospital, National Taiwan University Hospital and the Johns Hopkins Hospital.
Results: We demonstrated that loss of ARID1A expression was associated with ARID1A inactivating mutations in CCC (p= 0.0073). Specifically, all 9 CCCs harboring ARID1A mutations showed undetectable or very weak immunoreactivity while negative staining could also be observed in one of 3 CCCs with wild-type ARID1A. ARID1A immunoreactivity was undetectable or very week in 88 (59%) of 149 CCCs. There was no statistically significant difference of ARID1A negative and positive cases in terms of histopathological features (structural patterns, nuclear atypia, cystic vs. adenofibromatous), age, clinical sage, overall survival, and frequency of lymph node metastasis. However, we observed that loss of ARID1A expression correlated with lower chance of peritoneal dissemination (p<0.05).
Conclusions: In conclusion, this study provides the first analysis of ARID1A mutations and clinicopathological features and we demonstrate that mutations in ARID1A resulted in loss of ARID1A protein expression in CCC and there was no significant difference of ARID1A positive and negative cases in all the clinical parameters examined except for frequency of peritoneal dissemination.
Category: Gynecologic & Obstetrics
Monday, February 28, 2011 11:30 AM
Platform Session: Section D, Monday Morning