Combined Ezrin overexpression and E-cadherin downregulation as predictors of invasiveness, higher incidence of metastases, progression and poor prognosis in patients with cervical cancer

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Abstract

Background

Cervical cancer ranks the fourth in order among cancers in women worldwide. Management of patients with advanced and metastatic cervical cancer is not promising as such cancer could metastasize to lymph node early, which is considered a worse prognostic sign. With discovery and advancement in the field of molecular biology, the new era of research is focusing on discovering novel effective targets for therapy. Cancer spread or metastasis, which is responsible for the most serious and fatal outcome of most patients with cancer, is a multistep process and needs many interactions between malignant cells and nearby nonneoplastic areas. Ezrin, which is found at chromosome 6q25.2–q26 and is encoded by EZR gene, is an Ezrin/Radixin/Moesin family member. Ezrin is a linking protein of the cell membrane and the cytoskeleton that mediates the connection between both of them. So, Ezrin has essential role in cell division, motility, movement and other cellular functions. E-cadherin is a calcium-dependent glycoprotein that is found in normal epithelial cells. It could mediate cell adhesion, and also it maintains epithelial cells polarity and the cell structure integrity. Downregulation of E-cadherin-mediated normal cell adhesion is implicated in the process of cancer invasion and metastasis. However, the relation between the expressions of Ezrin and E-cad and relation between their expression and other clinical and pathological features in patients with cervical cancer have not been sufficiently clarified.

Aim

The aim of this research was to evaluate Ezrin and E-cadherin expressions in patients with cervical cancers, to correlate such expressions with pathological and clinical data of the patients and to explore their values in cancer invasiveness, metastases, progression, and prognosis of patients with cervical cancer.

Patients and methods

We have assessed Ezrin and E-cadherin expressions in sections from paraffin blocks of tissue obtained from 55 patients with cervical cancer, who were followed up for 3 years. Thereafter, we correlated the expressions of both markers with pathological criteria, clinical data, patients’ response to therapeutic modalities, cancer progression, relapse, and survival rates.

Results

High Ezrin expression and low E-cadherin expression were associated with cancer higher grade, presence of lymph node metastases, presence of lymphovascular invasion, advanced FIGO stage, (P<0.001), presence of distant metastases (P=0.003), more liability to malignant progression, poor therapy response, higher relapse rate (P<0.001) and poor disease-free survival and overall survival rates (P<0.001).

Conclusion

Ezrin overexpression is associated with downregulation of E-cadherin, and their corresponding expressions were related to more invasiveness liability, higher incidence of metastases, relapse after successive therapy, and poor prognosis in patients with cervical cancer.

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