4.6 Article

Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?

Journal

MODERN PATHOLOGY
Volume 25, Issue 6, Pages 885-892

Publisher

NATURE PUBLISHING GROUP
DOI: 10.1038/modpathol.2011.217

Keywords

ARID1A; BAF250a; endometriosis; ovarian carcinomas

Categories

Funding

  1. EMDO-Foundation
  2. Hartmann-Mueller-Foundation

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Mutations of the tumor-suppressor gene ARID1A result in the loss of protein expression of the BRG-associated factor 250a (BAF250a), a large subunit of transcription-regulating Human SWI/SNF complexes, which have an important role in the control of cell proliferation and tumor suppression. ARID1A mutations are particularly frequent in endometriosis-associated ovarian clear cell and endometrioid carcinomas, and were recently described as a possible key mechanism and early step in the transformation of endometriosis into cancer. Here, we examined the immunohistochemical expression pattern of BAF250a in a tissue microarray including 74 endometriosis and 30 endometrium samples. Ovarian cancer samples (n = 136) served as a control. Epithelial BAF250a expression was assessable in 90/104 (87%) and stromal BAF250a expression in 95/104 (91%) of the endometriosis, and endometrium cases due to lack of adequate tissue in some spots. Complete lack of BAF250a expression was observed in three endometriomas (n= 3/20, 15%) and one deep-infiltrating endometriosis sample (n = 1/22, 5%), but in none of the peritoneal endometriosis (n = 0/16) and eutopic endometrium samples (n= 0/30). A comparison of the mean immunoreactivity scores revealed a significantly lower expression rate of BAF250a in endometriomas compared with normal endometrium (P<0.0005), as well as peritoneal (P= 0.003) and deep-infiltrating endometriosis (P= 0.02). Our data demonstrates that a complete loss of BAF250a expression is observable in some endometriotic lesions, especially in endometriomas. In addition, we report that a partial loss of BAF250a expression is occurring in the form of cell clusters indicating a clonal loss of BAF250a expression in these cells. The loss of expression of the tumor-suppressor protein BAF250a in some endometriomas possibly indicates a risk of malignant transformation in these cases, which could be of importance in the determination of individual treatment strategies. However, its role and value as a prognostic parameter in endometriosis needs to be further studied. Modern Pathology (2012) 25, 885-892; doi:10.1038/modpathol.2011.217; published online 3 February 2012

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