Significance of Mortalin Expression in Gastric Cancer with Normal P53.

25 Background: Gastric cancer still has the highest morbidity rate and the second highest mortality rate. As chemotherapy confers only a minimal survival advantage, the prognosis of patients with advanced or recurrent gastric cancer remains poor. Studying the mechanisms and underlying molecules that drives gastric cancer malignant, could contribute to finding a remedy for gastric cancer. Mortalin is a heat non-inducible member of the heat shock protein 70 family. Mortalin binds to p53 and prevents p53 from entering the nucleus, as well as cell stress. To understand the significance of mortalin in gastric cancer, we investigated the expression of mortalin and p53. Methods: The expression of mortalin and p53 were examined by immunohistochemical staining of 182 clinical samples of gastric cancer. Results: Mortalin-positive and aberrant-p53-positive samples were found in 75.2% and 62.6% of cases, respectively. Mortalin-positive tumors were deeper in invasion and had more lymph node and liver metastases compared with mortalin-negative tumors (p < 0.01, p < 0.05, respectively). Mortalin-positive tumors had worse prognosis compared with mortalin-negative tumors (p = 0.035). Moreover, in tumors with normal p53 expression, mortalin-positive tumors had especially worse prognosis compared with mortalin-negative tumors (p = 0.013). With multivariate analysis, mortalin expression appeared to be an independent prognostic factor in gastric cancer with expression of normal p53 (p = 0.0174). Conclusions: Mortalin has a great impact on gastric cancer with normal p53. Therefore, mortalin is a target molecule for treatment of gastric cancer, as well as a promising prognostic factor, especially in tumors with normal p53.