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

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

Research output: Contribution to journalArticle

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).

Original languageEnglish (US)
Pages (from-to)471-478
Number of pages8
JournalJournal of Pathology
Volume199
Issue number4
DOIs
StatePublished - Apr 1 2003

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Keywords

  • Atypical endometrial hyperplasia
  • Catenin
  • catenin mutation
  • E-cadherin
  • Endometrial cancer
  • P-cadherin

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Moreno-Bueno, G., Hardisson, D., Sarrió, D., Sánchez, C., Cassia, R., Prat, J., Herman, J. G., Esteller, M., Matías-Guiu, X., & Palacios, J. (2003). Abnormalities of E- and P-cadherin and catenin (β-, γ-catenin, and p120ctn) expression in endometrial cancer and endometrial atypical hyperplasia. Journal of Pathology, 199(4), 471-478. https://doi.org/10.1002/path.1310