期刊
INTERNATIONAL JOURNAL OF GYNECOLOGICAL PATHOLOGY
卷 31, 期 4, 页码 297-303出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/PGP.0b013e31823f8482
关键词
ARID1A; Ovarian borderline tumor
资金
- NIH/NCI [CA165807, CA129080]
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, which has been reported in a third to a half of cases. 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 their expression have been studied in gynecologic cancer, the expression pattern of ARID1A has not been investigated in ovarian atypical proliferative (borderline) tumors. 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. We observed loss of ARID1A staining in 8 (33%) of 24 seromucinous tumors. In contrast, ARID1A staining was retained in all the other 32 tumors except in 1 endometrioid tumor (P < 0.01). Mutational analysis was performed on 2 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% to 57% of endometrioid and clear cell carcinomas but only rarely in serous tumors. In summary, these tumors often contain endocervical-type mucinous epithelium, but they typically display papillary architecture, unlike most endocervical neoplasms, and their immunophenotype is different from both endocervical and serous tumors. Moreover, they frequently contain ciliated cells, endometrial-type cells, cells with abundant eosinophilic cytoplasm, and hobnail-shaped cells, all of which can be found in endometrioid tumors. The loss of expression of ARID1A and the presence of inactivating mutations of the ARID1A gene further link this tumor to endometrioid and clear cell tumors, as does the frequent association with endometriosis. Accordingly, we suggest designating these tumors atypical proliferative (borderline) papillary mullerian tumors'' as this designation more accurately reflects their clinicopathologic, immunohistochemical, and molecular genetic features.
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