Nicotinamide N‐methyltransferase in nonmelanoma skin cancers

Abstract

Background Squamous cell carcinoma (SCC) and basal cell carcinoma (BCC) represent the most common forms of nonmelanoma skin cancers (NMSCs). Although successful treatment of these neoplasms is based on surgical excision, an increasing number of BCCs relapses and many SCCs display high rates of recurrence and metastasis. Nicotinamide N‐methyltransferase (NNMT) is a cytosolic enzyme, which was found to be upregulated in different solid tumours. However, there are no data regarding enzyme expression in NMSCs. The aim of this study was therefore to evaluate the potential involvement of NNMT in BCCs and SCCs. Materials and methods Immunohistochemical analyses were carried out on 40 BCC cases and 39 SCC cases, to evaluate enzyme expression in tumour and surrounding healthy margins. Moreover, the relationship between NNMT intratumour levels and clinico‐pathological parameters were explored. Results Nicotinamide N‐methyltransferase was found to be overexpressed in BCCs compared with control tissues, while a significant enzyme downregulation was detected in SCCs with respect to corresponding healthy margins. In addition, NNMT levels were negatively related to aggressiveness of both BCCs (distinguishing between infiltrative and nodular tumours) and SCCs (considering head and neck forms and tumours of the extremities and trunk). Conclusions These evidences seem to demonstrate that the different NNMT dysregulation detected in BCC and SCC may be the result of important biological traits distinctively characterizing these two forms within NMSCs. In addition, enzyme levels seem to be inversely correlated with tumour aggressiveness, thus suggesting the potential suitability of the enzyme as a prognostic biomarker for both neoplasms.

Paraoxonase‐2: A potential biomarker for skin cancer aggressiveness

“…PON2 expression in tumour and control tissues was assessed by immunohistochemical analyses 21 . 5 µm sections were cut from FFPE blocks, mounted on poly‐L‐lysine‐coated glass slides, deparaffinized in xylene, rehydrated in a graded alcohol series and treated with EnVision FLEX Target Retrieval Solution High pH (cat.…”

“…PON2 expression in tumour and control tissues was assessed by immunohistochemical analyses. 21 a 3% H 2 O 2 solution for 7 minutes to inhibit endogenous peroxidase and blocked with 5% Normal Goat Serum (cat. X0907, lot.…”

Beyond Nicotinamide Metabolism: Potential Role of Nicotinamide N-Methyltransferase as a Biomarker in Skin Cancers

“…A subsequent study explored the role of NNMT also in NMSC. A total of 79 specimens (40 BCC and 39 SCC cases) were subjected to immunohistochemical analysis to evaluate the enzyme expression levels, with the healthy tissue margins used as a control [ 94 ]. In the BCC cohort, NNMT expression was significantly higher in tumor specimens than in normal tissue margins.…”

The Utility of Nicotinamide N-Methyltransferase as a Potential Biomarker to Predict the Oncological Outcomes for Urological Cancers: An Update

“…In fact, NNMT overexpression has been reported for many solid tumors, including gastrointestinal neoplasms [40][41][42][43][44][45][46][47][48], lung [49][50][51][52], oral [53][54][55][56][57][58][59], esophageal [60,61], nasopharyngeal [62] and thyroid [63][64][65] cancers, as well as ameloblastoma [66] and glioblastoma multiforme [67]. Significant NNMT upregulation was recently found in epithelial neoplasms [68][69][70][71][72][73] and in association with cancer stem cells (CSCs) [74][75][76][77][78]. Regarding women's cancers, enzyme overexpression was detected in breast [79][80][81], endometrial [82], cervical [83] and ovarian [84] cancer.…”