Overexpression of metadherin/MTDH is associated with an aggressive phenotype and a poor prognosis in invasive breast cancer

Abstract

Metadherin (MTDH) plays functional roles in the tumorigenesis and tumor progression of various cancers. This study investigated the associations between MTDH and the clinicopathological features in primary breast carcinomas to clarify the role of MTDH in the phenotypes and prognosis of breast cancer. A total of 195 primary invasive breast cancer samples were evaluated. The MTDH DNA copy number and MTDH mRNA expression were analyzed by quantitative genomic polymerase chain reaction (PCR) and quantitative reverse transcriptase PCR. MTDH protein expression was analyzed by immunohistochemistry. A positive correlation was found between the expression of MTDH protein and mRNA expression and the MTDH DNA copy number. MTDH overexpression was significantly associated with a high nuclear grade, negative estrogen receptor (ER) and progesterone receptor (PR) expression, high Ki67 index, poor disease-free survival (P=0.0001), poor distant metastasis-free survival (P=0.009), and poor overall survival (P=0.0101). MTDH overexpression showed a particularly negative impact on the prognosis in node-negative patients. A multivariate analysis showed MTDH overexpression to be independently associated with a poor disease-free survival rate [HR 3.45, 95% confidence interval (CI) 1.69-6.84, P=0.0010] and a poor distant metastasis-free survival rate (HR 2.39, 95% CI 1.08-5.01, P=0.0319). MTDH overexpression contributes to an aggressive phenotype, thus leading to a poor prognosis for primary invasive breast cancer.