# NNMT overexpression is an adverse prognostic factor in uterine leiomyosarcoma

## TL;DR

NNMT overexpression is linked to worse outcomes in uterine leiomyosarcoma, a rare and aggressive cancer, and may help distinguish it from benign tumors.

## Contribution

This is the first study to investigate NNMT expression in uterine leiomyosarcoma and its correlation with prognosis.

## Key findings

- NNMT expression was significantly higher in uterine leiomyosarcoma compared to benign tissues.
- High NNMT levels were an independent predictor of worse recurrence-free survival in uLMS.
- NNMT overexpression may help differentiate uLMS from uterine leiomyoma preoperatively.

## Abstract

Uterine leiomyosarcomas (uLMS) are extremely rare high-grade tumors with a poor prognosis. Their etiopathogenesis remains largely unknown. The uterus is the most frequent site for LMS. uLMS and uterine leiomyoma (uLM) must frequently be differentiated in patients with a uterine mass. Nicotinamide N-methyltransferase (NNMT), a cytoplasmic protein, is involved in the progression and spread of a variety of cancer types. The expression of NNMT in a mesenchymal malignancy was not examined previously. This study represents the first investigation into NNMT expression in uLMS, uLM and benign uterine myometrium and correlates NNMT overexpression with worse prognosis in uLMS.

The expression of NNMT was investigated by immunohistochemistry on formalin-fixed paraffin-embedded tissue of uLMS in 31 patients, uLM in seven patients and benign myometrial in 31 patients.

The expression of NNMT in uLMS was markedly higher than in uLM and normal myometrial tissue (p < 0.001). The expression of NNMT in early stage uLMS was lower than in advanced stage disease (p = 0.034). NNMT expression was an independent prognostic factor in predicting recurrence-free survival in uLMS (p = 0.037).

NNMT can aid in the preoperative differentiation of uLMS and uLM. The consequences of NNMT overexpression, such as the activation and inactivation of oncoproteins and tumor suppressor proteins, respectively, as well as the enrichment of the cancer stem cell population, overlap with the major mechanisms responsible for poor prognosis in mesenchymal tumors. NNMT may be investigated further in the context of antitumor treatment in patients with mesenchymal malignancies.