Mod Pathol  2000 Oct;13(10):1066-71 

Mutational analysis of the CTNNB1 and APC genes in uterine endometrioid
carcinoma.

Schlosshauer PW, Pirog EC, Levine RL, Ellenson LH.

Department of Pathology, Joan and Sanford I. Weill Medical College of Cornell
University, New York, USA.

Despite recent studies, the molecular genetic events responsible for the
development of uterine endometrioid carcinoma (UEC) remain incompletely
characterized. Mutations in the beta-catenin (CTNNB1) gene have been recently
reported in a small percentage of UECs and in the endometrioid variant of
ovarian carcinoma suggesting that the Wnt signal transduction pathway is
involved in the development of female genital tract tumors with endometrioid
morphology. The Wnt pathway is a critical pathway in the development of
colorectal cancer (CRC) with mutations occurring in the beta-catenin (CTNNB1) or
adenomatous polyposis coli (APC) genes in 10 to 15% and 85% of cases,
respectively. Because UEC and CRC share other molecular genetic alterations and
histologic features and previous studies of UEC have not reported an analysis of
the APC gene, we chose to further elucidate the role of the Wnt pathway in UEC.
To this end, we analyzed 32 cases of UEC for mutations of the CTNNB1 and APC
genes. Mutations of CTNNB1 were present in six of 32 (18%) cases: four grade 1
carcinomas, one grade 2, and one grade 3 carcinoma. Five missense mutations were
identified, three involving Ser/Thr phosphorylation sites and two adjacent to a
Ser phosphorylation site. One case contained a deletion encompassing codons 34
to 37, which includes a Ser phosphorylation site. No mutations resulting in
truncation of the APC protein were found. Our results support a role for the Wnt
signaling pathway via mutation of CTNNB1, but not APC, in the development of a
subset of UECs.

PMID: 11048799 [PubMed - indexed for MEDLINE]