Schult D, Hölsken A, Buchfelder M, Schlaffer S-M, Siegel S, Kreitschmann-Andermahr I, Fahlbusch R, Buslei R
Department of Neuropathology, Friedrich-Alexander University Erlangen-Nürnberg (FAU), Erlangen, Germany.
Pituitary. 2015 Aug;18(4):465-73. doi: 10.1007/s11102-014-0597-2.
α-Internexin (INA) is a class IV neuronal intermediate filament protein that maintains the morphogenesis of neurons. It is expressed in developing neuroblasts and represents the major component of the cytoskeleton in cerebellar granule cells of adult central nervous system tissue. Data concerning INA expression in the human frontal pituitary lobe and related adenomas (PA) is missing.
Using immunohistochemistry we examined the distribution pattern of INA in a large cohort of 152 PA, 11 atypical PA, 4 pituitary carcinomas and 20 normal pituitaries (overall n = 187). Quantity of INA protein expression was semi-quantitatively evaluated and grouped into five categories (0 = 0%; 1 = >0-5%; 2 = >5-35%; 3 = >35-80%; 4 = >80% of cells).
Cellular staining intensity of INA appeared significantly higher in gonadotropinomas (Go, n = 62), null cell adenomas (NC, n = 7) and thyrotropinomas (TSHomas, n = 7) compared to the other tumor subtypes (p ≤ 0.001). Furthermore, Go and NC showed a peculiar pseudorosette-like staining pattern surrounding blood vessels in 85.5% (59/69) of cases. Interestingly, areas exhibiting homogenous INA staining were often associated with oncocytic cell changes and decreased immunohistochemically detectable hormone expression. Only 8.5% (8/94) of other PA showed a comparable INA distribution (p ≤ 0.001).
Go, NC as well as TSHomas exhibit high levels of intracellular INA protein indicating neuronal transdifferentiation. A possible impact on pathogenesis and endocrine activity needs further investigation.
α-中间丝蛋白（INA）是一种IV类神经元中间丝蛋白，可维持神经元的形态发生。它在发育中的成神经细胞中表达，是成年中枢神经系统组织小脑颗粒细胞细胞骨架的主要成分。关于INA在人类额叶垂体叶及相关腺瘤（PA）中的表达数据尚缺。
我们采用免疫组织化学方法检测了152例PA、11例非典型PA、4例垂体癌和20例正常垂体（共187例）的大样本队列中INA的分布模式。对INA蛋白表达量进行半定量评估，并分为五类（0 = 0%；1 = >0 - 5%；2 = >5 - 35%；3 = >35 - 80%；4 = >80%的细胞）。
与其他肿瘤亚型相比，促性腺激素瘤（Go，n = 62）、无功能细胞腺瘤（NC，n = 7）和促甲状腺激素瘤（TSH瘤，n = 7）中INA的细胞染色强度明显更高（p≤0.001）。此外，85.5%（59/69）的Go和NC病例显示血管周围有特殊的假菊形团样染色模式。有趣的是，显示均匀INA染色的区域常与嗜酸性细胞改变及免疫组化可检测到的激素表达降低相关。其他PA中只有8.5%（8/94）表现出类似的INA分布（p≤0.001）。
Go、NC以及TSH瘤表现出高水平的细胞内INA蛋白，提示神经元转分化。其对发病机制和内分泌活性的潜在影响需要进一步研究。
