NOVA2 expression in pituitary gland and in functioning and non-functioning pituitary adenomas: a preliminary study

Purpose: Pituitary adenomas (PAs) are generally benign tumors with varying clinical presentations. While functioning PAs (FPAs) secrete hormones leading to distinct endocrine disorders, non-functioning PAs (NFPAs) often manifest with mass effect symptoms. Current medical therapies for PAs have limited efficacy, particularly for NFPAs. This highlights the need for new diagnostic and therapeutic targets. This study aimed to investigate the expression of Neuro-Oncological Ventral Antigen 2 (NOVA2), a factor involved in alternative splicing, in normal pituitary glands and PAs, to evaluate its potential as a novel therapeutic target. Methods: Tissue samples from 12 PA patients (9 NFPAs and 3 FPAs) and 8 normal pituitary glands were collected. Immunohistochemical analysis was performed to assess NOVA2 expression. Semi-quantitative evaluation of NOVA2 staining was conducted using Histoscore. Results: NOVA2 was expressed in the endothelial cells of both PAs and normal pituitary glands, with higher expression in PAs. Notably, NOVA2 was present in PA cells regardless of adenoma type, while normal pituitary epithelial cells were negative for NOVA2 expression. There was no statistically significant difference in NOVA2 expression between FPAs and NFPAs. Conclusions: This is the first study to demonstrate that NOVA2 is expressed in PA cells but not in normal pituitary epithelial cells. These findings suggest that NOVA2 could serve as a potential target for diagnostic and therapeutic strategies in PAs, especially considering the lack of specific biomarkers and effective medical therapies for these tumors. Further research with a larger sample size is warranted to validate these preliminary findings.