Nicotinamide N-methyltransferase expression and its association with phospho-Akt, p53 expression, and survival in high-grade endometrial cancer

Abstract

Background/aim: Nicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies. NNMT expressionhas not been previously studied in endometrial cancer (EC). Increased phospho-Akt (pAkt) levels in response to NNMT overexpressionhave been reported in in vitro studies of different cancer types. We assayed NNMT expression in primary and metastatic high-grade ECand investigated the relationship of NNMT with p53, pAkt, and survival.Materials and methods: NNMT, pAkt, and p53 expressions were assayed in 100 tissue samples of benign endometria, primary EC, andmetastatic EC by immunohistochemistry.Results: The NNMT immunoreactivity score was significantly higher in primary high-grade EC than benign endometrial tissue (P =0.001). NNMT expression in metastatic tissue was significantly higher than in primary cancer (P < 0.001). Metastatic stromal NNMTexpression was significantly higher than that of the adjacent tumor and stroma adjacent to the primary tumor. p53 expression inthe primary tumor showed a significant positive correlation with omental NNMT and pAkt expression. NNMT expression was alsocorrelated with pAkt expression in metastatic tissue. NNMT overexpression in metastatic tissue was associated with decreased survival(P = 0.039).Conclusion: This study suggests that NNMT may promote cancer progression and that NNMT overexpression is associated withaberrant p53 expression, pAkt, and poor survival. NNMT’s role in cancer progression could make it a target of EC therapy.