Loss of ARID1A/BAF250a-expression in endometriosis: a biomarker for risk of carcinogenic transformation?
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.
Department of Gynecology, University Hospital Zurich, Zurich, Switzerland.
Eleftherios P
EP
Samartzis
Nicolas
N
Samartzis
Aurelia
A
Noske
André
A
Fedier
Rosmarie
R
Caduff
Konstantin J
KJ
Dedes
Daniel
D
Fink
Patrick
P
Imesch
D000328:Adult; D014408:Biomarkers, Tumor / Q000032:analysis; D000077216:Carcinoma, Ovarian Epithelial; D016022:Case-Control Studies; D002471:Cell Transformation, Neoplastic / Q000737:chemistry* / Q000473:pathology; D016009:Chi-Square Distribution; D004268:DNA-Binding Proteins; D015536:Down-Regulation; D004715:Endometriosis / Q000378:metabolism* / Q000473:pathology; D004847:Epithelial Cells / Q000737:chemistry; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000737:chemistry* / Q000473:pathology; D009687:Nuclear Proteins / Q000032:analysis*; D010051:Ovarian Neoplasms / Q000737:chemistry* / Q000473:pathology; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D017154:Stromal Cells / Q000737:chemistry; D013557:Switzerland; D046888:Tissue Array Analysis; D014157:Transcription Factors / Q000032:analysis*; D055815:Young Adult
C112476:ARID1A protein, human; D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors