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Loss of BAF250a (ARID1A) is frequent in high-grade endometrial carcinomas

Authors

  • Kimberly C Wiegand,

    1. The Center for Translational and Applied Genomics (CTAG) at the British Columbia (BC) Cancer Agency, Vancouver, BC, Canada
    2. University of British Columbia, Vancouver, BC, Canada
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  • Anna F Lee,

    1. University of British Columbia, Vancouver, BC, Canada
    2. Vancouver General Hospital, Vancouver, BC, Canada
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  • Osama M Al-Agha,

    1. Vancouver General Hospital, Vancouver, BC, Canada
    2. Genetic Pathology Evaluation Centre (GPEC, Vancouver, BC, Canada
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  • Christine Chow,

    1. Genetic Pathology Evaluation Centre (GPEC, Vancouver, BC, Canada
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  • Steve E Kalloger,

    1. University of British Columbia, Vancouver, BC, Canada
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  • David W Scott,

    1. The Center for Translational and Applied Genomics (CTAG) at the British Columbia (BC) Cancer Agency, Vancouver, BC, Canada
    2. British Columbia (BC) Cancer Agency, Centre for Lymphoid Cancer, Vancouver, BC, Canada
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  • Christian Steidl,

    1. The Center for Translational and Applied Genomics (CTAG) at the British Columbia (BC) Cancer Agency, Vancouver, BC, Canada
    2. British Columbia (BC) Cancer Agency, Centre for Lymphoid Cancer, Vancouver, BC, Canada
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  • Sam M Wiseman,

    1. University of British Columbia, Vancouver, BC, Canada
    2. St. Paul's Hospital, Department of Surgery, Vancouver, BC, Canada
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  • Randy D Gascoyne,

    1. The Center for Translational and Applied Genomics (CTAG) at the British Columbia (BC) Cancer Agency, Vancouver, BC, Canada
    2. British Columbia (BC) Cancer Agency, Centre for Lymphoid Cancer, Vancouver, BC, Canada
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  • Blake Gilks,

    1. University of British Columbia, Vancouver, BC, Canada
    2. Vancouver General Hospital, Vancouver, BC, Canada
    3. Genetic Pathology Evaluation Centre (GPEC, Vancouver, BC, Canada
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  • David G Huntsman

    Corresponding author
    1. The Center for Translational and Applied Genomics (CTAG) at the British Columbia (BC) Cancer Agency, Vancouver, BC, Canada
    2. University of British Columbia, Vancouver, BC, Canada
    3. Genetic Pathology Evaluation Centre (GPEC, Vancouver, BC, Canada
    • Centre for Translational and Applied Genomics, Room 3427, BC Cancer Agency, 600 West 10th Avenue, Vancouver, BC, Canada.
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  • No conflicts of interest were declared.

Abstract

Mutation of the ARID1A gene and loss of the corresponding protein BAF250a has recently been described as a frequent event in clear cell and endometrioid carcinomas of the ovary. To determine whether BAF250a loss is common in other malignancies, immunohistochemistry (IHC) for BAF250a was performed on tissue microarrays (TMAs) in more than 3000 cancers, including carcinomas of breast, lung, thyroid, endometrium, kidney, stomach, oral cavity, cervix, pancreas, colon and rectum, as well as endometrial stromal sarcomas, gastrointestinal stromal tumours, sex cord-stromal tumours and four major types of lymphoma (diffuse large B cell lymphoma, primary mediastinal B cell lymphoma, mantle cell lymphoma and follicular lymphoma). We found that BAF250a loss is frequent in endometrial carcinomas but infrequent in other types of malignancies, with loss observed in 29% (29/101) of grade 1 or 2 and 39% (44/113) of grade 3 endometrioid carcinomas of the endometrium, 18% (17/95) of uterine serous carcinomas and 26% (6/23) of uterine clear cell carcinomas. Since endometrial cancers showed BAF250a loss, we stained whole tissue sections for BAF250a expression in nine cases of atypical hyperplasia and 10 cases of atypical endometriosis. Of the nine cases of complex atypical endometrial hyperplasia, all showed BAF250a expression; however, of 10 cases of atypical endometriosis (the putative precursor lesion for ovarian clear cell and endometrioid carcinoma), one case showed loss of staining for BAF250a in the atypical areas, with retention of staining in areas of non-atypical endometriosis. This was the sole case that recurred as an endometrioid carcinoma, indicating that BAF250a loss may be an early event in carcinogenesis. Since BAF250a loss is seen in endometrial carcinomas at a rate similar to that seen in ovarian carcinomas of clear cell and endometrioid type, and is uncommon in other malignancies, we conclude that loss of BAF250a is a particular feature of carcinomas arising from endometrial glandular epithelium. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.

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