Low expression of mixed lineage kinase domain-like protein is associated with poor prognosis in ovarian cancer patients

Abstract

Background: Mixed lineage kinase domain-like protein (MLKL) was initially identified as a key receptor interacting protein 3 downstream component of tumor-necrosis-factor-induced necrosis. In this study, we characterized the expression of MLKL in ovarian carcinomas and evaluated the prognostic value of MLKL in patients with ovarian cancer. Materials and methods: The ovarian cancer tissue specimens were collected from 153 patients diagnosed as primary ovarian cancer after operation at The Second Xiangya Hospital from January 2005 to December 2008. Immunohistochemistry was performed for MLKL and the protein expression score was quantified using an established scoring system. Kaplan-Meier survival curves were generated for disease-free survival (DFS) and overall survival (OS) for all patients. MLKL expression levels were correlated with DFS and OS using univariate and multivariate Cox regression analysis. Results: Seventy-five patients (49%) were defined as having high MLKL expression and 67 patients (43.7%) had >80% of cells staining for MLKL. Remarkably, low MLKL expression was significantly associated with decreased DFS (median 40 months versus 25 months, P=0.0282) and OS (median 43 months versus 28 months, P=0.0032). In multivariate analysis, retained significance was also observed. Conclusion: Low MLKL expression was significantly associated with both decreased DFS and OS in patients with primary ovarian cancer. MLKL expression may serve as a potential prognostic marker in patients with ovarian cancer.