The Expression And Prognosis Of EHD2 In Breast Carcinoma

Objective: Breast cancer is the most common invasive tumor diagnosed in women worldwide. Breast cancer accounts for 23 %(1.38 million) of new cancer diagnoses. Until recently, the majority of patients with breast cancer were treated with surgery firstly followed by chemotherapy, hormonal therapy and radiation therapy according to the pathologic. However, the general effect is not very satisfactory treatment. While looking for breast cancer progression of internal mechanism, through selective targeted drugs, find out the new molecular targets for the prevention, diagnosis and treatment of breast cancer is particularly important. However, the mechanism that regulates tumorigenesis is not well understood. EHD2( EH- domain containing protein 2) was identified as an membrane transport regulatory proteins containing 543 amino acid residues. EHD2 appears to connect endocytosis to the actin cytoskeleton through interactions of its N-terminal domain with membranes and its C-terminal EH domain. EHD2 was an important member of the EHDs family, which appears to regulate receptors in a broad range of human organs and tissues, further bolstering their physiological signi?cance. It is found that EHD is linked to proteins that regulate the actin cytoskeleton interactions, small GTP enzymes, and some cell surface receptors that can carry the corresponding ligands to the plasma membrane.EHD2 was shown to be implicated as a tumor suppressor gene in glioma tumors, but there was not any in-depth study of its mechanism. Ki-67 is a nuclear antigen associated with proliferating cells. It is considered as one of the most reliable indicators to detect cell proliferation activity. It can reflect the proliferation activity of normal and diseased cells, and can be used to differentiate benign and malignant diseases. Ki-67 has been widely used in various cancers including breast cancer.In the present study, therefore, we investigated the intimate relationship between highly invasive potential of breast cancer and the phenotype showing simultaneous expression of EHD2 and expression of Ki-67.Methods: Immunohistochemical analysis were performed in 95 human breast carcinoma samples and tissues adjacent to carcinoma to detect EHD2 expression in these organizations, compared with the proliferation of antigen(Ki-67),the data were correlated with clinic pathologic features.Results: We found that the expression of EHD2 was positively related with Ki-67 expression(P<0.01) and EHD2 expression correlated significantly with histologic grade(P =0.001), lymph node status(P =0.006), ER status(P =0.013). Kaplan-Meier analysis revealed that survival curves of low versus high expressers of EHD2 and Ki-67 showed a highly significant separation in human breast cancer(P <0.01). When a multivariate Cox proportional hazard model was constructed(including age, histologic grade, tumor size, ER status, PR status, EHD2 and Ki-67 expressions), EHD2 as well as Ki-67 were the strongest independent prognostic predictor of overall survival.Conclusions: EHD2 expression may be prognostic for patients with invasive breast carcinomas, which associated with Ki-67 expression. EHD2 may not only become a new diagnostic and prognostic marker but also serve as a potential therapeutic strategy for the management of breast cancer and/or other malignant tumors.