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(American Journal of Pathology. 2002;160:1229-1238.)
© 2002 American Society for Investigative Pathology

Short Communication

Role of ß-Catenin/T-Cell Factor-Regulated Genes in Ovarian Endometrioid Adenocarcinomas

Yali Zhai^*, Rong Wu^*, Donald R. Schwartz^*, Danielle Darrah^*, Heather Reed^*, Frank T. Kolligs, Marvin T. Nieman, Eric R. Fearon^* and Kathleen R. Cho^*

From the Departments of Pathology,^* InternalMedicine, and HumanGenetics, and The Comprehensive CancerCenter, The University of Michigan MedicalSchool, Ann Arbor, Michigan

In various cancers, inactivating mutations in the adenomatous polyposis coli or Axin tumor suppressor proteins or activating mutations in ß-catenin’s amino-terminal domain elevate ß-catenin levels, resulting in marked effects on T-cell factor (TCF)-regulated transcription. Several candidate ß-catenin/TCF-regulated genes in cancer have been proposed. Expression of a few of these genes has been studied in primary human cancers, but most studies have focused on colon cancers and not on other cancer types that harbor mutational defects in adenomatous polyposis coli, AXIN, or ß-catenin. Mutations leading to ß-catenin deregulation are found in nearly half of ovarian endometrioid adenocarcinomas (OEAs). We report here on the expression of 6 candidate ß-catenin/TCF-regulated genes in a panel of 44 primary OEAs, more than a third of which carry demonstrable defects in ß-catenin regulation. Using quantitative assays of gene expression, we found significantly elevated expression of the MMP-7, CCND1 (Cyclin D1), CX43 (Connexin 43), PPAR-, and ITF2 genes in OEAs with deregulated ß-catenin. This correlation was not observed for c-myc, another putative ß-catenin/TCF-regulated gene. Immunohistochemical studies confirmed that overexpression of cyclin D1 and MMP-7 was highly associated with nuclear accumulation of ß-catenin and mutational defects of the Wnt/ß-catenin/TCF-signaling pathway. Our findings indicate cyclin D1, MMP-7, connexin 43, PPAR-, and ITF-2, likely play important roles in the pathogenesis of those OEAs that manifest defects in ß-catenin regulation.

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