TY - JOUR
T1 - Abnormalities of the APC/β-catenin pathway in endometrial cancer
AU - Moreno-Bueno, Gema
AU - Hardisson, David
AU - Sánchez, Carolina
AU - Sarrió, David
AU - Cassia, Raúl
AU - García-Rostán, Ginesa
AU - Prat, Jaime
AU - Guo, Mingzhou
AU - Herman, James G.
AU - Matías-Guiu, Xavier
AU - Esteller, Manel
AU - Palacios, José
PY - 2002/11/14
Y1 - 2002/11/14
N2 - 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
AB - 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
KW - β catenin mutations
KW - γ-catenin
KW - APC promoter hypermethylation
KW - AXIN1
KW - AXIN2
KW - Endometrial cancer
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U2 - 10.1038/sj.onc.1205924
DO - 10.1038/sj.onc.1205924
M3 - Article
C2 - 12439748
AN - SCOPUS:18744368086
SN - 0950-9232
VL - 21
SP - 7981
EP - 7990
JO - Oncogene
JF - Oncogene
IS - 52
ER -