Abstract
Background/aimNicotinamide N-methyltransferase (NNMT) is an enzyme that is overexpressed in malignancies. NNMT expression has not been previously studied in endometrial cancer (EC). Increased phospho-Akt (pAkt) levels in response to NNMT overexpression have been reported in in vitro studies of different cancer types. We assayed NNMT expression in primary and metastatic high-grade EC and investigated the relationship of NNMT with p53, pAkt, and survival.Materials and methodsNNMT, pAkt, and p53 expressions were assayed in 100 tissue samples of benign endometria, primary EC, and metastatic EC by immunohistochemistry.ResultsThe 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 NNMT expression was significantly higher than that of the adjacent tumor and stroma adjacent to the primary tumor. p53 expression in the primary tumor showed a significant positive correlation with omental NNMT and pAkt expression. NNMT expression was also correlated with pAkt expression in metastatic tissue. NNMT overexpression in metastatic tissue was associated with decreased survival (P = 0.039).ConclusionThis study suggests that NNMT may promote cancer progression and that NNMT overexpression is associated with aberrant p53 expression, pAkt, and poor survival. NNMT’s role in cancer progression could make it a target of EC therapy.
Highlights
Endometrial adenocarcinoma is the most frequent form of uterine cancer, which is the leading gynecological cancer in countries with adequate cervical cancer prevention programs [1]
The Nicotinamide N-methyltransferase (NNMT) immunoreactivity score was significantly higher in primary high-grade endometrial cancer (EC) than benign endometrial tissue (P = 0.001)
NNMT expression was correlated with pAkt expression in metastatic tissue
Summary
Endometrial adenocarcinoma is the most frequent form of uterine cancer, which is the leading gynecological cancer in countries with adequate cervical cancer prevention programs [1]. High-grade endometrial cancer (EC) comprises a histological subtype of tumors that are more aggressive in nature than low-grade tumors and include serous, clear cell, grade 3 endometrioid adenocarcinomas, undifferentiated carcinomas, and carcinosarcomas. High-grade tumors make up only 10%–20% of EC, they are responsible for a disproportionate 40% of mortality [2,3]. Nicotinamide N-methyltransferase (NNMT) is a cytosolic enzyme that is overexpressed in a variety of human malignancies including lung cancer [4], This is the first study to investigate NNMT expression in primary and metastatic EC. We sought to assay NNMT expression in benign endometrial tissue, high-grade endometrial neoplasms, and matched metastatic omental tissue. We attempted to investigate the relationship of NNMT with p53 and phospho-Akt (pAkt) in metastatic EC. The association of disease-specific survival (DSS) with NNMT expression was analyzed
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