Loss of ARID1A expression correlates with stages of tumor progression in uterine endometrioid carcinoma.
ARID1A is a recently identified tumor suppressor that functions in chromatin remodeling. Inactivating mutations of ARID1A and loss of its expression most frequently occur in ovarian clear cell carcinoma, ovarian endometrioid carcinoma, and uterine endometrioid carcinoma. In this study, we performed a detailed immunostaining analysis of ARID1A in 246 cases including benign endometrium and endometrioid carcinoma at different stages of progression. Special attention was paid to recording intratumoral heterogeneity of clonal loss of ARID1A immunoreactivity. All normal endometria (n=51) and endometrial polyps (n=14) retained ARID1A expression. Among complex atypical hyperplasias (n=38), 16% exhibited clonal loss of ARID1A, but none showed complete loss. Among low-grade endometrioid carcinomas (n=88), 25% exhibited complete loss and 24% exhibited clonal loss. In contrast, 44% of high-grade endometrioid carcinomas (n=55) showed complete loss of ARID1A, and 9% exhibited clonal loss. We found that 19 high-grade carcinomas also contained concurrent low-grade carcinomas. In the high-grade areas, 63% exhibited complete loss and 11% exhibited clonal loss, whereas in the low-grade areas, 37% exhibited complete loss and 42% clonal loss. In 5 of these 19 cases, progressive loss of ARID1A from retention or clonal loss to complete loss was observed between the low-grade and high-grade areas. Overall, the percentage of complete ARID1A loss increased from 0% in complex atypical hyperplasia, to 25% in low-grade endometrioid carcinoma, to 44% in high-grade endometrioid carcinoma. These findings suggest that loss of ARID1A expression, presumably due to mutation, plays an important role in tumor progression of uterine endometrioid carcinoma.
*Department of Pathology, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan †Department of Pathology, Johns Hopkins Medical Institutions, Baltimore, MD ‡Seirei Mikatahara General Hospital, Hamamatsu, Japan.
Tsui-Lien
TL
Mao
Laura
L
Ardighieri
Ayse
A
Ayhan
Kuan-Ting
KT
Kuo
Chen-Hsuan
CH
Wu
Tian-Li
TL
Wang
Ie-Ming
IeM
Shih
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000032:analysis*; D001706:Biopsy; D018269:Carcinoma, Endometrioid / Q000737:chemistry* / Q000473:pathology; D016022:Case-Control Studies; D004268:DNA-Binding Proteins; D018450:Disease Progression; D015536:Down-Regulation; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D060787:Neoplasm Grading; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D013997:Time Factors; D014157:Transcription Factors / Q000032:analysis*; D014594:Uterine Neoplasms / Q000737:chemistry* / Q000473:pathology
C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors