The clinicopathological significance of Mortalin overexpression in invasive ductal carcinoma of breast

Abstract

Background: Mortalin/GRP75 is a ubiquitous mitochondrial chaperone which related to the cytosolic heat shock protein 70 (HSP70), and plays a role in carcinogenesis. This study aims to investigate the Mortalin expression in breast cancer and its correlation with the outcome of the patients with breast cancer. Methods: A total of 155 invasive ductal carcinoma of breast patients with strict follow-up, 52 ductal carcinoma in situ (DCIS) and 45 adjacent non-tumor breast tissues were selected for immunohistochemical (IHC) staining of Mortalin protein. The localization of Mortalin protein was detected in MDA-MB231 breast cancer cells using immunofluorescence (IF) staining. The correlations between overexpression of Mortalin and the clinical features of patients with breast cancer were evaluated using chi-square test and Fisher's exact tests. The survival rates were calculated by the Kaplan-Meier method, and the relationship between prognostic factors and patient survival was also analyzed by the Cox proportional hazard models. Results: Mortalin protein showed a mainly cytoplasmic staining pattern in breast cancers by using IHC staining in paraffin embedded breast cancer tissues and IF staining in MDA-MB231 breast cancer cells. The strongly positive rate of Mortalin protein was 63.9 % (99/155) in invasive ductal carcinoma of breast and was significantly higher than in DCIS 34.6 % (18/52) and adjacent non-tumor tissues 15.6 % (7/45). Overexpression of Mortalin was closely correlated with histological grade, clinical stage, lymph node metastasis, lower disease free survival (DFS) and overall survival (OS) rates of patients with breast cancer. Moreover, multivariate analysis suggested that Mortalin emerged as a significant independent prognostic factor along with clinical stage and Her2 expression status in patients with breast cancer. Conclusions: Mortalin is upregulated in breast cancer, and may be a useful poor prognostic biomarker as well as a potential therapeutic target for patients with breast cancer.