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Mod Pathol. 2014 Jan;27(1):128-34. doi: 10.1038/modpathol.2013.107. Epub 2013 Jun 14.

Ovarian and endometrial endometrioid carcinomas have distinct CTNNB1 and PTEN mutation profiles.

Author information

1
Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada.
2
1] Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada [2] Department of Computer Science, University of British Columbia, Vancouver, BC, Canada.
3
Division of Gynecology Oncology, Princess Margaret Cancer Centre, Toronto, ON, Canada.
4
Division of Gynaecologic Oncology, Department of Obstetrics and Gynaecology, Vancouver General Hospital, University of British Columbia, Vancouver, BC, Canada.
5
Department of Pathology and Laboratory Medicine, Vancouver General Hospital and University of British Columbia, Vancouver, BC, Canada.
6
Department of Obstetrics and Gynecology, College of Medicine, Ohio State University, Columbus, OH, USA.
7
1] Department of Pathology and Laboratory Medicine, University of British Columbia, BC Cancer Agency, Centre for Translational and Applied Genomics, Vancouver, BC, Canada [2] Department of Molecular Oncology, BC Cancer Agency, Vancouver, BC, Canada.

Abstract

Ovarian endometrioid carcinomas and endometrial endometrioid carcinomas share many histological and molecular alterations. These similarities are likely due to a common endometrial epithelial precursor cell of origin, with most ovarian endometrioid carcinomas arising from endometriosis. To directly compare the mutation profiles of two morphologically similar tumor types, endometrial endometrioid carcinomas (n=307) and ovarian endometrioid carcinomas (n=33), we performed select exon capture sequencing on a panel of genes: ARID1A, PTEN, PIK3CA, KRAS, CTNNB1, PPP2R1A, TP53. We found that PTEN mutations are more frequent in low-grade endometrial endometrioid carcinomas (67%) compared with low-grade ovarian endometrioid carcinomas (17%) (P<0.0001). By contrast, CTNNB1 mutations are significantly different in low-grade ovarian endometrioid carcinomas (53%) compared with low-grade endometrial endometrioid carcinomas (28%) (P<0.0057). This difference in CTNNB1 mutation frequency may be reflective of the distinct microenvironments; the epithelial cells lining an endometriotic cyst within the ovary are exposed to a highly oxidative environment that promotes tumorigenesis. Understanding the distinct mutation patterns found in the PI3K and Wnt pathways of ovarian and endometrial endometrioid carcinomas may provide future opportunities for stratifying patients for targeted therapeutics.

PMID:
23765252
PMCID:
PMC3915240
DOI:
10.1038/modpathol.2013.107
[Indexed for MEDLINE]
Free PMC Article

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