The neuronal intermediate filament protein α-internexin is differentially expressed in endocrine active versus clinically nonfunctioning pituitary adenomas

Abstract

Objective: α-internexin is a class IV neuronal intermediate filament (IF) protein that maintains the morphogenesis of neurons. Thereby, it often cooperates with the heterogeneous group of neurofilaments, but is also able to form independent structural networks. The protein is expressed in developing neuroblasts and represents the major component of the cytoskeleton in small interneurons and cerebellar granule cells of adult Central Nervous System tissue. Data concerning α-internexin expression in the human frontal pituitary lobe and related adenomas is missing. Materials and Methods: Using immunohistochemistry (monoclonal mouse anti-α-internexin antibody, clone 2E3, Invitrogen, Darmstadt) we examined the distribution pattern of α-internexin in a series of 21 normal pituitaries, and a large cohort of pituitary adenomas and two carcinomas. Expression of α-internexin was semiquantitatively evaluated and scored in five groups (0%; > 0 – 5%; > 5 – 35%; > 35% – 80%; > 80% of cells). We used SPSS for statistical analysis. Results: α-internexin is differentially expressed in endocrine active versus clinically nonfunctioning pituitary tumors. Except of the subgroup of thyrotropin-producing adenomas (n = 8), quantity and staining intensity of α-internexin expression were significantly higher in clinically nonfunctioning tumors (n = 83; p < 0,001), especially in gonadotropin-producing cases (n = 60). Endocrine inactive adenomas showed a peculiar pseudorosette-like staining pattern surrounding blood vessels in 64% (53/83) of samples. Thereby, areas exhibiting homogenous α-internexin distribution were often associated with oncocytic cell change and decreased immunohistochemically detectable hormone expression. Less than 5% (4/88) of endocrine active cases and no pituitary frontal lobe (0/21) showed comparable distribution patterns (p < 0,001). Conclusion: Clinically nonfunctioning adenomas exhibit high levels of the neuronal IF protein α-internexin indicating neuronal differentiation. The impact on the tumorigenic process and endocrine activity needs further investigation.