Abnormalities of E- and P-cadherin and catenin (β-, γ-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia

Authors

  • Gema Moreno-Bueno,

    1. Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
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  • David Hardisson,

    1. Department of Pathology, Hospital Universitario La Paz, Madrid, Spain
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  • David Sarrió,

    1. Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
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  • Carolina Sánchez,

    1. Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
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  • Raúl Cassia,

    1. Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
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  • Jaime Prat,

    1. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona and Hospital Universitari Arnau de Vilanova, Lleida, Spain
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  • James G Herman,

    1. Johns Hopkins Oncology Center, Baltimore, Maryland, USA
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  • Manel Esteller,

    1. Laboratory of Cancer Epigenetics, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain
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  • Xavier Matías-Guiu,

    1. Department of Pathology, Hospital de la Santa Creu i Sant Pau, Barcelona and Hospital Universitari Arnau de Vilanova, Lleida, Spain
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  • José Palacios

    Corresponding author
    1. Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Madrid, Spain.
    • Laboratory of Breast and Gynaecological Cancer, Molecular Pathology Programme, Centro Nacional de Investigaciones Oncológicas (CNIO), Melchor Fernández Almagro 3, 28029 Madrid, Spain.
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Abstract

Abnormal expression of cadherins and catenins plays a critical role in the initiation and progression of multiple human tumours. This study aimed to evaluate the immunoreactivity of E- and P-cadherin, β- and γ-catenin, and p120ctn in premalignant and malignant endometrial lesions and to correlate their membranous expression with clinicopathological features. In addition, we examined whether or not LOH and promoter hypermethylation of the CDH1 gene were associated with E-cadherin expression and clinicopathological variables. Finally, we studied the frequency of β-catenin mutations in premalignant endometrial lesions. Immunohistochemical staining was performed in 21 atypical endometrial hyperplasias (AEHs), 95 endometrioid carcinomas (EECs), and 33 non-endometrioid carcinomas (NEECs). Reduced E-cadherin expression was observed in 57.8% of the cases, being more frequent in NEECs (87.1%, p = 0.001) and carcinomas of more advanced stage (85.7% of stage III–IV carcinomas, p = 0.01). LOH of CDH1 gene was found in 57.1% of NEECs but only in 22.5% of EECs (p = 0.011) and showed a trend towards association with reduced E-cadherin expression (p = 0.089). CDH1 promoter hypermethylation was found in 21.2% of endometrial carcinomas but was not associated with clinicopathological or immunohistochemical variables. Reduced expression of β- and γ-catenin and p120ctn was found in 76.1%, 94.3%, and 63.6% of the cases, respectively, being more frequent in lesions with reduced E-cadherin expression. In addition, β-catenin, but not γ-catenin or p120ctn expression, was associated with the histology of the lesion, since it was reduced in 35% of AEHs, 80.3% of EECs, and 96.9% of NEECs (p = 0.000). Mutations in exon 3 of the β-catenin gene, associated with β-catenin nuclear expression, were detected in 3 (14.0%) AEH, a frequency similar to that previously reported in this series of ECs. Finally, upregulation of P-cadherin was observed in 28.6% of cases. This alteration was associated with the histology of the lesion, since it was found in 9.5% of AEHs, 27.7% of EECs, and 46.2% of NEECs (p = 0.021). Copyright © 2003 John Wiley & Sons, Ltd.

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