Expression Pattern of Neuronal Intermediate Filament α-internexin in Anterior Pituitary Gland and Related Tumors

Overview

Journal Pituitary

Specialty Endocrinology

Date 2014 Sep 20

PMID 25236435

Citations 6

Authors

D Schult

A Holsken

M Buchfelder

S-M Schlaffer

S Siegel

I Kreitschmann-Andermahr

R Fahlbusch

R Buslei

Affiliations

Soon will be listed here.

Abstract

Purpose: 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.

Methods: 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).

Results: 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).

Conclusion: 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.

Citing Articles

Targeting tumor innervation: premises, promises, and challenges.

Li X, Peng X, Yang S, Wei S, Fan Q, Liu J Cell Death Discov. 2022; 8(1):131.

PMID: 35338118 PMC: 8956600. DOI: 10.1038/s41420-022-00930-9.

Many Voices in a Choir: Tumor-Induced Neurogenesis and Neuronal Driven Alternative Splicing Sound Like Suspects in Tumor Growth and Dissemination.

Dlamini Z, Mathabe K, Padayachy L, Marima R, Evangelou G, Syrigos K Cancers (Basel). 2021; 13(9).

PMID: 33946706 PMC: 8125307. DOI: 10.3390/cancers13092138.

DNA Methylation Influences miRNA Expression in Gonadotroph Pituitary Tumors.

Boresowicz J, Kober P, Rusetska N, Maksymowicz M, Paziewska A, Dabrowska M Life (Basel). 2020; 10(5).

PMID: 32413978 PMC: 7281098. DOI: 10.3390/life10050059.

Progenitors from the central nervous system drive neurogenesis in cancer.

Mauffrey P, Tchitchek N, Barroca V, Bemelmans A, Firlej V, Allory Y Nature. 2019; 569(7758):672-678.

PMID: 31092925 DOI: 10.1038/s41586-019-1219-y.

Genetic aspects of pituitary carcinoma: A systematic review.

Yang Z, Zhang T, Gao H Medicine (Baltimore). 2016; 95(47):e5268.

PMID: 27893664 PMC: 5134857. DOI: 10.1097/MD.0000000000005268.

References

Ikota H, Kinjo S, Yokoo H, Nakazato Y . Systematic immunohistochemical profiling of 378 brain tumors with 37 antibodies using tissue microarray technology. Acta Neuropathol. 2006; 111(5):475-82. DOI: 10.1007/s00401-006-0060-1. View

Asa S, Ezzat S . The pathogenesis of pituitary tumors. Annu Rev Pathol. 2009; 4:97-126. DOI: 10.1146/annurev.pathol.4.110807.092259. View

Fliegner K, KAPLAN M, Wood T, Pintar J, Liem R . Expression of the gene for the neuronal intermediate filament protein alpha-internexin coincides with the onset of neuronal differentiation in the developing rat nervous system. J Comp Neurol. 1994; 342(2):161-73. DOI: 10.1002/cne.903420202. View

Nagaishi M, Suzuki A, Nobusawa S, Yokoo H, Nakazato Y . Alpha-internexin and altered CIC expression as a supportive diagnostic marker for oligodendroglial tumors with the 1p/19q co-deletion. Brain Tumor Pathol. 2013; 31(4):257-64. DOI: 10.1007/s10014-013-0168-7. View

Lu X, Chen X, Huang L, Zhu C, Gu Y, Ye S . Anti-alpha-internexin autoantibody from neuropsychiatric lupus induce cognitive damage via inhibiting axonal elongation and promote neuron apoptosis. PLoS One. 2010; 5(6):e11124. PMC: 2886066. DOI: 10.1371/journal.pone.0011124. View

Krammer H, Karahan S, Sigge W, KUHNEL W . Immunohistochemistry of markers of the enteric nervous system in whole-mount preparations of the human colon. Eur J Pediatr Surg. 1994; 4(5):274-8. DOI: 10.1055/s-2008-1066117. View

Lindner J, Rivier J, Vale W, Pavlou S . Regulation of pituitary glycoprotein alpha-subunit secretion after administration of a luteinizing hormone-releasing hormone antagonist in normal men. J Clin Endocrinol Metab. 1990; 70(4):1219-24. DOI: 10.1210/jcem-70-4-1219. View

Zhu X, Lee K, Asa S, Ezzat S . Epigenetic silencing through DNA and histone methylation of fibroblast growth factor receptor 2 in neoplastic pituitary cells. Am J Pathol. 2007; 170(5):1618-28. PMC: 1854956. DOI: 10.2353/ajpath.2007.061111. View

KAPLAN M, Chin S, Fliegner K, Liem R . Alpha-internexin, a novel neuronal intermediate filament protein, precedes the low molecular weight neurofilament protein (NF-L) in the developing rat brain. J Neurosci. 1990; 10(8):2735-48. PMC: 6570287. View

10.

Scheithauer B, Horvath E, Kovacs K, Lloyd R, Stefaneanu L, Buchfelder M . Prolactin-producing pituitary adenoma and carcinoma with neuronal components--a metaplastic lesion. Pituitary. 2000; 1(3-4):197-205. DOI: 10.1023/a:1009913303109. View

11.

Eaker E, Sallustio J . The distribution of novel intermediate filament proteins defines subpopulations of myenteric neurons in rat intestine. Gastroenterology. 1994; 107(3):666-74. DOI: 10.1016/0016-5085(94)90113-9. View

12.

Dannies P . A possible differentiation of anterior pituitary cells in collagen gels into neurons. Cell Tissue Res. 1986; 244(1):21-6. DOI: 10.1007/BF00218377. View

13.

Melmed S . Mechanisms for pituitary tumorigenesis: the plastic pituitary. J Clin Invest. 2003; 112(11):1603-18. PMC: 281651. DOI: 10.1172/JCI20401. View

14.

Cairns N, Uryu K, Bigio E, Mackenzie I, Gearing M, Duyckaerts C . alpha-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases. Acta Neuropathol. 2004; 108(3):213-23. PMC: 3516855. DOI: 10.1007/s00401-004-0882-7. View

15.

Ohara O, Gahara Y, Miyake T, Teraoka H, Kitamura T . Neurofilament deficiency in quail caused by nonsense mutation in neurofilament-L gene. J Cell Biol. 1993; 121(2):387-95. PMC: 2200107. DOI: 10.1083/jcb.121.2.387. View

16.

Rajasalu T, Teesalu K, Janmey P, Uibo R . Demonstration of natural autoantibodies against the neurofilament protein alpha-internexin in sera of patients with endocrine autoimmunity and healthy individuals. Immunol Lett. 2004; 94(1-2):153-60. DOI: 10.1016/j.imlet.2004.05.002. View

17.

Mokhtari K, Ducray F, Kros J, Gorlia T, Idbaih A, Taphoorn M . Alpha-internexin expression predicts outcome in anaplastic oligodendroglial tumors and may positively impact the efficacy of chemotherapy: European organization for research and treatment of cancer trial 26951. Cancer. 2011; 117(13):3014-26. DOI: 10.1002/cncr.25827. View

18.

Zhou Y, Zhang X, Klibanski A . Genetic and epigenetic mutations of tumor suppressive genes in sporadic pituitary adenoma. Mol Cell Endocrinol. 2013; 386(1-2):16-33. PMC: 3943596. DOI: 10.1016/j.mce.2013.09.006. View

19.

Ho D, Hsu C, Ting L, Chiang H . The clinicopathological characteristics of gonadotroph cell adenoma: a study of 118 cases. Hum Pathol. 1997; 28(8):905-11. DOI: 10.1016/s0046-8177(97)90005-8. View

20.

Chen J, Hersmus N, Van Duppen V, Caesens P, Denef C, Vankelecom H . The adult pituitary contains a cell population displaying stem/progenitor cell and early embryonic characteristics. Endocrinology. 2005; 146(9):3985-98. DOI: 10.1210/en.2005-0185. View