Analysis of pituitary adenoma expression patterns suggests a potential role for the NeuroD1 transcription factor in neuroendocrine tumor-targeting therapies

Abstract

NeuroD1’s roles in the pathogenesis of pituitary adenomas and in the biology of the normal adult pituitary gland have been insufficiently researched. Much of the work investigating its expression patterns has yielded contradictory results. Objective: morphological study of NeuroD1 transcription factor expression in different types of pituitary adenomas and in normal adult human pituitary glands. Materials and methods: This study analyzed 48 pituitary adenomas and nine normal pituitary glands. In all cases, immunohistochemical study was performed with antibodies to NeuroD1, 6 hormones of adenohypophysis, Ki-67, and CK7. We used confocal laser scanning microscopy, electron microscopy and electron immunocytochemistry. Results: NeuroD1 expression was detected in all cases of plurihormonal adenomas, mammosomatotropinomas, corticotropinomas, prolactinomas, gonadotropinomas, null-cell pituitary adenomas, and in normal pituitary glands. The average numbers of NeuroD1 expressing cells in normal adenohypophysis specimens were significantly lower than in the adenomas overall (p=0.006). NeuroD1 expression was confirmed by several methods (in prolactinomas, by double stain immunohistochemistry; in mammosomatotropinomas, by double stain immunohistochemistry, confocal laser scanning microscopy, and electron immunocytochemistry; and in somatotropinomas, by electron immunocytochemistry). Conclusion: Immunohistochemistry, confocal microscopy, and double label electron immunocytochemistry confirmed NeuroD1’s key role in the pathogenesis of pituitary tumors, regardless of their hormonal state. Its expression level in pituitary adenomas is significantly higher than in the normal pituitary gland and has no reliable correlation with any studied hormones or Ki-67. These findings suggest that NeuroD1 should be investigated further as a potential molecular target in tumor-targeting therapies.