Abnormalities of the APC/β-catenin pathway in endometrial cancer

Gema Moreno-Bueno, David Hardisson, Carolina Sánchez, David Sarrió, Raúl Cassia, Ginesa García-Rostán, Jaime Prat, Mingzhou Guo, James G. Herman, Xavier Matías-Guiu, Manel Esteller, José Palacios

Research output: Contribution to journalArticle

Abstract

The activation of the APC/β-catenin signalling pathway due to β-catenin mutations has been implicated in the development of a subset of endometrial carcinomas (ECs). However, up to 25% of ECs have β-catenin nuclear accumulation without evidence of β-catenin mutations, suggesting alterations of other molecules that can modulate the Wnt pathway, such as APC, γ-catenin, AXIN1 and AXIN2. We investigated the expression pattern of β- and γ-catenin in a group of 128 endometrial carcinomas, including 95 endometrioid endometrial carcinomas (EECs) and 33 non-endometrioid endometrial carcinomas (NEECs). In addition, we evaluated the presence of loss of heterozygosity and promoter hypermethylation of the APC gene and mutations in the APC, β- and γ-catenin, AXIN1, AXIN2, and RAS genes, and phospho-Akt expression. No APC mutations were detected but LOH at the APC locus was found in 24.3% of informative cases. APC promoter 1A hypermethylation was observed in 46.6% of ECs, and was associated with the endometrioid phenotype (P=0.034) and microsatellite instability (P=0.008). Neither LOH nor promoter hypermethylation of APC was associated with nuclear catenin expression. Nuclear β-catenin expression was found in 31.2% of EECs and 3% of NEECs (P=0.002), and was significantly associated with β-catenin gene exon 3 mutations (P

Original languageEnglish (US)
Pages (from-to)7981-7990
Number of pages10
JournalOncogene
Volume21
Issue number52
DOIs
StatePublished - Nov 14 2002

Keywords

  • β catenin mutations
  • γ-catenin
  • APC promoter hypermethylation
  • AXIN1
  • AXIN2
  • Endometrial cancer

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics

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  • Cite this

    Moreno-Bueno, G., Hardisson, D., Sánchez, C., Sarrió, D., Cassia, R., García-Rostán, G., Prat, J., Guo, M., Herman, J. G., Matías-Guiu, X., Esteller, M., & Palacios, J. (2002). Abnormalities of the APC/β-catenin pathway in endometrial cancer. Oncogene, 21(52), 7981-7990. https://doi.org/10.1038/sj.onc.1205924