Ting-Tai Yen1, Tsutomu Miyamoto2, Shiho Asaka3, M Herman Chui4, Yeh Wang5, Shiou-Fu Lin5, Rebecca L Stone1, Amanda N Fader1, Ryoichi Asaka2, Hiroyasu Kashima6, Tanri Shiozawa6, Tian-Li Wang5, Ie-Ming Shih7, Edward J Tanner1. 1. Kelly Gynecologic Oncology Service, Department of Gynecology and Obstetrics, Johns Hopkins School of Medicine, Baltimore, MD, United States of America. 2. Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan; Gynecologic Pathology Laboratroy, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America. 3. Departments of Oncology and Pathology, Johns Hopkins Medical institutions, Baltimore, MD, United States of America; Department of Diagnostic Pathology, Shinshu University Hospital, Matsumoto, Japan; Department of Laboratory Medicine, Shinshu University School of Medicine, Matsumoto, Japan. 4. Gynecologic Pathology Laboratroy, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America. 5. Gynecologic Pathology Laboratroy, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America; Departments of Oncology and Pathology, Johns Hopkins Medical institutions, Baltimore, MD, United States of America. 6. Department of Obstetrics and Gynecology, Shinshu University School of Medicine, Matsumoto, Japan. 7. Gynecologic Pathology Laboratroy, Department of Gynecology and Obstetrics, Johns Hopkins Medical Institutions, Baltimore, MD, United States of America; Departments of Oncology and Pathology, Johns Hopkins Medical institutions, Baltimore, MD, United States of America. Electronic address: ishih@jhmi.edu.
Abstract
OBJECTIVES: Inactivating somatic mutations of ARID1A, a chromatin remodeling gene, are common in endometrioid endometrial carcinoma (EEC) but rare in complex atypical hyperplasia (CAH). Our objectives were to determine the clinical significance of ARID1A loss during tumor progression from CAH to EEC and to assess its role as a predictive cancer biomarker. METHODS: In cohort A, ARID1A immunoreactivity was evaluated in endometrial sampling (biopsy/curettage) specimens showing CAH to determine whether ARID1A expression correlates with the presence of EEC at subsequent hysterectomy. In cohort B, ARID1A immunoreactivity was evaluated in the hysterectomy specimens with concurrent CAH and EEC to assess for the concordance of ARID1A expression in both components. RESULTS: In cohort A, loss of ARID1A immunoreactivity was identified in the endometrial sampling specimen of 31% of patients undergoing hysterectomy for a preoperative diagnosis of CAH. EEC was identified in the hysterectomy specimen of 94% of patients with loss of ARID1A in the endometrial sampling specimen while only 15% of patients with retained ARID1A expression (P < 0.0001). No association was observed between ARID1A expression and demographic characteristics. In cohort B, 14 (31%) of 45 patients with concurrent CAH/EEC in their hysterectomy specimens had complete loss of ARID1A expression in the EEC components. Among these 14 patients, 50% also had loss of ARID1A immunoreactivity in the CAH component. CONCLUSIONS: ARID1A immunostaining may correlate with malignant transformation and the presence of concurrent EEC in patients with CAH identified at pre-hysterectomy endometrial sampling. Further investigation to determine the potential utility of ARID1A expression as a tissue biomarker is warranted.
OBJECTIVES: Inactivating somatic mutations of ARID1A, a chromatin remodeling gene, are common in endometrioid endometrial carcinoma (EEC) but rare in complex atypical hyperplasia (CAH). Our objectives were to determine the clinical significance of ARID1A loss during tumor progression from CAH to EEC and to assess its role as a predictive cancer biomarker. METHODS: In cohort A, ARID1A immunoreactivity was evaluated in endometrial sampling (biopsy/curettage) specimens showing CAH to determine whether ARID1A expression correlates with the presence of EEC at subsequent hysterectomy. In cohort B, ARID1A immunoreactivity was evaluated in the hysterectomy specimens with concurrent CAH and EEC to assess for the concordance of ARID1A expression in both components. RESULTS: In cohort A, loss of ARID1A immunoreactivity was identified in the endometrial sampling specimen of 31% of patients undergoing hysterectomy for a preoperative diagnosis of CAH. EEC was identified in the hysterectomy specimen of 94% of patients with loss of ARID1A in the endometrial sampling specimen while only 15% of patients with retained ARID1A expression (P < 0.0001). No association was observed between ARID1A expression and demographic characteristics. In cohort B, 14 (31%) of 45 patients with concurrent CAH/EEC in their hysterectomy specimens had complete loss of ARID1A expression in the EEC components. Among these 14 patients, 50% also had loss of ARID1A immunoreactivity in the CAH component. CONCLUSIONS:ARID1A immunostaining may correlate with malignant transformation and the presence of concurrent EEC in patients with CAH identified at pre-hysterectomy endometrial sampling. Further investigation to determine the potential utility of ARID1A expression as a tissue biomarker is warranted.
Authors: Yemin Wang; Valerie Lan Tao; Chae Young Shin; Clara Salamanca; Shary Yuting Chen; Christine Chow; Martin Köbel; Susana Ben-Neriah; David Farnell; Christian Steidl; Jessica N Mcalpine; C Blake Gilks; David G Huntsman Journal: PLoS One Date: 2020-10-14 Impact factor: 3.240
Authors: Mike R Wilson; Jake J Reske; Julie Koeman; Marie Adams; Niraj R Joshi; Asgerally T Fazleabas; Ronald L Chandler Journal: Cells Date: 2022-03-15 Impact factor: 6.600