The Expression Of Ezrin And Its Clinical Significance In Cervical Cancer

Background: The most damaging change during cancer progression is the switch from a locally growing tumor to a metastatic killer. Tumor progression and metastasis are common phenomena in cancer. There are many factors related to this switch and is believed to involve numerous alterations that allow tumor cells to complete the complex series of events including invasion of the surrounding stroma, angiogenesis, transport of nutrients and provision of routes to enter the circulatory system then metastasize distant sites. During the process of invasion there are several "molecules" that may assist cancer cells to locate the favorable organ to metastasize, to interact with endothelial cells, to migrate through the endothelium and subsequently penetrate structures including matrix and vascular endothelium.Recent studies showed that the membrane-linking protein Ezrin is the most important member of the ERM (Ezrin/radixin/moesin). It regulates the determinationand maintenance of cell shape, cell adhesion to the extracellular matrix, cell-cell interaction, receptor tyrosine-kinase signaling, signal transduction pathway and interactions with the Akt-mediated cellular apoptotic machinery. Ezrin plays an important role in cell motility, cell polarity, citokinesis, phagocytosis, and stabilization of intercellular junctions; participates in membrane trafficking pathways, and integration of membrane transport with signaling pathways. Ezrin is highly expressed in several types of human cancers and correlated between its expression and histopathological data as well as patient outcome, which have been shown in rhabdomyosarcoma, osteosarcoma, brain hemangioblastoma, uterine endometroid adenocarcinoma, uveal malignant melanoma, renal adenocarcinoma, human pancreatic adenocarcinoma, prostate cancer, serous ovarian carcinoma and breast cancer.Cervical cancer is the second most common cancer in women worldwide, and becomes the most prevalent female malignancy and the leading cause of death by cancer in developing countries. However, studies of the expression of Ezrin have not yet been reported on human cervical cancer. This study assesses a group of samples of cervical cancer in order to evaluate Ezrin expression and its relation with histopathological data. The expression of Ezrin in cervical intraepithelial neoplasia (CIN) and normal tissue was also studied as controls.Material and methods: Immunohistochemical analysis was used to detect the expression of Ezrin in 100 hysterectomy specimens including cervical cancers (60 cases), CIN (20 cases) and benign epithelium (20 cases) from the Department of pathology of the Women's Hospital, Zhejiang University. Ezrin expression was assessed by immunohistochemistry using mouse monoclonal antibody against Ezrin (Ab-1; Neomarker, Lab Vision Corp, CA, USA). Tissue samples were scored for the intensity of Ezrin expression and the scores were compared among the clinical pathologic parameters including the patient age, FIGO stage, tissue type, histological grade, stroma invasion, lymph-node metastasis and lymph-vascular space involvement (LVSI) of cervical cancer.Results: Expression of Ezrin was faint in normal cervical epithelium. Moderate or strong expression was detected in 19 of 20 cervical intraepithelial neoplasia (CIN) specimens and just 1 sample showed weak expression in this group. In cervical cancer, the expression varied from strong (56.6% of samples) to moderate (33.3%), weak (10%) or faint (0%). Ezrin expression was significantly higher than that in CIN and normal control (P= 0.001 and 0.002). Immunoreactivity showed that Ezrin is only present in the cytoplasm of epithelial cells, especially near the cytoplasmic membrane, while stromal tissue remained unstained; the cytoplasmic staining was diffuse in all cases. Stronger expression of Ezrin was significantly associated with outer one-third stroma invasion (P = 0.005). No correlations were found with the age of patients (P = 0.393), FIGO stage (P = 0.121), tissue type (P= 0.536), histological grade (P = 0.243), LVSI (P = 0.919), and lymph node metastasis (P = 0.097).Conclusions:1. There are gradual increased expressions of Ezrin from normal throughout CIN to cancer of the cervix, indicating that over-expression of Ezrin plays a role in carcinogenesis of the cervix.2. The expression of Ezrin is higher in outer one-third stroma invasion, suggesting that higher Ezrin expression is probably associated with poorer prognosis of cervical cancer.