E-cadherin and β-catenin expression in early stage cervical carcinoma: A tissue microarray study of 147 cases

Background: The disruption of intercellular adhesions is an important component of the acquisition of invasive properties in epithelial malignancies. Alterations in the cell-cell adhesion complex, E-Cadherin/β-Catenin, have been implicated in the oncogenesis of carcinomas arising from various anatomic sites and have been correlated with adverse clinico-pathologic parameters. In this study, the authors investigated the immunohistochemical expression of E-Cadherin and β-Catenin in a cohort of early stage cervical cancers to determine its prognostic significance and to investigate differences between the three major histological subtypes. Patients and methods: A tissue microarray of 147 cases of FIGO stage 1A and 1B cervical carcinomas [96 squamous cell carcinomas (SCC), 35 adenocarcinomas (AC), 12 adenosquamous carcinomas (ASQ), 4 miscellaneous types] was constructed from our archived surgical pathology files and stained with monoclonal antibodies to E-Cadherin and β-Catenin. Cases were scored by multiplying the intensity of staining (1 to 3 scale) by the percentage of cells stained (0-100%) for a potential maximum score of 300. For both markers, "preserved" expression was defined as bright membranous staining with a score of 200 or above. "Impaired" expression included any of the following: negative staining, a score less than 200, or exclusively cytoplasmic or nuclear delocalization. Results: Impaired expression of β-Catenin was found in 85.7%, 66.7%, & 58.3% of AC, SCC & ASQ respectively. Impaired expression of E-Cadherin was found in 94.3%, 86.5% & 100% of cases of AC, SCC, & ASQ respectively. The differences between the histologic subtypes were not significant. For the whole cohort, a comparsion of cases showing impaired versus preserved of E-Cadherin and β-Catenin expression showed no significant differences with respect to recurrence free survival, overall survival, patient age, histologic grade, and frequency of lymphovascular invasion or lymph node involvement. There was no correlation between the status of both markers for all three histological subtypes (overall spearman correlation co-efficient r = 0.12, p = 0.14). Conclusion: Impairment of E-Cadherin and β-Catenin expression is very frequent in early stage cervical cancers, and alterations in the E-Cadherin/β-Catenin cell adhesion complex are therefore likely involved in the pathogenesis of cervical carcinomas even at their earliest stages. None of the three major histological subtypes of cervical carcinoma (SCC, ADCA, ADSQ) is significantly more likely than the others to show impairment in E-Cadherin and β-Catenin expression. Overall, the expression of both markers does not significantly correlate with clinico-pathological parameters of prognostic significance.