Endocervical-Type Mucinous Borderline Tumors Are Related to Endometrioid Tumors Based on Mutation and Loss of Expression of ARID1A
Chen Hsuan Wu, Tsui-Lien Mao, Russell Vang, Ayse Ayhan, Robert J Kurman, Ie-Ming Shih. Johns Hopkins Medical Institutions, Baltimore, MD; National Taiwan University College of Medicine, Taipei, Taiwan
Background: Nongastrointestinal-type mucinous borderline tumors have been described as displaying endocervical and serous differentiation and hence have been termed “endocervical-type” mucinous borderline tumors, “mixed epithelial papillary cystadenoma of borderline malignancy of mullerian type” or “atypical proliferative seromucinous tumors”. A striking feature of these tumors is their frequent association with endometriosis. This is an unusual finding as pure endocervical and serous tumors are not usually associated with endometriosis. ARID1A is a recently identified tumor suppressor, which frequently loses its expression and is mutated in endometrium-related carcinomas including ovarian clear cell, ovarian endometrioid and uterine endometrioid carcinomas. Although ARID1A mutations and expression have been studied in gynecological cancer, its expression pattern has not been investigated in ovarian atypical proliferative (borderline) tumors.
Design: In this study, we analyzed ARID1A expression in serous, gastrointestinal-type and endocervical-type (seromucinous) mucinous, and endometrioid atypical proliferative (borderline) tumors using immunohistochemistry and performed mutational analysis in selected cases.
Results: We observed loss of ARID1A staining in 8 (35%) of 23 seromucinous tumors. In contrast, ARID1A staining was retained in all the other 32 tumors except in one endometrioid tumor (p<0.01). Mutational analysis was performed on two representative seromucinous tumors, which showed complete loss of ARID1A. Both tumors harbored somatic inactivating ARID1A mutations. Previous studies have reported loss of expression and/or mutation of ARID1A in 30-57% of endometrioid and clear cell carcinomas but only rarely in serous tumors.
Conclusions: We showed a significantly higher frequency of loss of ARID1A expression in endocervical-type (seromucinous) tumors, presumably due to mutation, than the other histologic types, suggesting that they are molecularly related to endometrioid and clear cell tumors. If other investigators confirm our findings, we propose designating them “atypical proliferative (borderline) papillary endometrioid tumors of mixed cell type” based on their morphologic and molecular genetic features.
|serous||endometrioid||gastrointestinal type mucinous||seromucinous|
|cases with loss of ARID1A staining||0||1||0||8|
|total case number||13||8||12||23|
|% of cases with loss of staining||0||13||0||35|