Beta-HLH transcription factors are involved in the ontogenesis of neural/neuroendocrine cells, and may play a role in the pathogenesis of neuroendocrine tumours. Neurogenin 2 (Ngn2) is expressed by the developing mouse pituitary. After preliminary data indicating its expression in the normal human pituitary, we have studied its phenotypic expression in normal and adenomatous pituitary tissues.
Methods: Fifty-two pituitary adenomas (PA) 23 clinically non-secreting (CNS) and 29 clinically secreting (CS) (13 GH-, 8 PRL-, 6 ACTH- and 2 TSH-secreting PA, respectively) - and 4 normal pituitaries (NP) were studied. Ngn2 transcripts were determined by realtime qRT-PCR and compared to beta-actin transcripts, using Taqman on-demand assays (Applied Biosystems). Immunohistochemistry was performed on 21 PA and 2 NP, using a rabbit polyclonal antibody (Chemicon). Mouse monoclonal antibodies for pituitary hormones (Dako) were used for co-localization experiments.
Results: Ngn2 transcripts were observed in all NP and 39/52 (75%) of PA, with a higher frequency in CS versus CNS PA (89.6% vs 56.5%, χ2=7.51, P=0.006). Accordingly, Ngn2 levels were higher in CS than in CNS PA (P=0.006, Mann-Whitney). Only a subset of PA (11/52=21.1%) were found to moderately overexpress Ngn2 as compared to NP: 8 were CS and 3 were CNS, including 2 silent-secreting PA. Nuclear immunopositivity for Ngn2 was detected in scattered cells of the NP, co-localizing with most pituitary hormones, and in 17/21 PA (14/15 CNS and 3/6 CNS, respectively). No significant correlation was found between Ngn2 expression and tumour volume, invasiveness or Ki-67 labelling index.
Conclusions: Ngn2 is expressed by the NP and a significant subset of PA. Its preferential expression by CS PA, the lack of significant overexpression or correlation with tumour aggressiveness, suggest that Ngn2 may contribute to maintain a differentiated secreting phenotype in PA but plays no role in pituitary tumorigenesis itself.