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Immunohistochemical expression of nestin in the non-tumorous hypophysis and in pituitary neoplasms

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Abstract

The aim of the present work was to investigate whether nestin, a member of the intermediate filament family, is immunohistochemically expressed in the non-tumoral human hypophysis and pituitary neoplasms. Twenty-three normal pituitaries and 125 pituitary neoplasms were included. The tissues were formalin-fixed and paraffin embedded. The neoplasms were identified on hematoxylin–eosin stained sections and were classified by immunohistochemistry as well as electron microscopy. For immunohistochemistry, the streptavidin–biotin–peroxidase complex method was applied using appropriate controls. Several corticotrophs in the autopsy obtained pituitaries showed cytoplasmic nestin immunopositivity. No nestin immunoreactivity was found in other cell types in non-tumorous adenohypophyses and in the cells of various pituitary adenomas. Nestin was, however, expressed in a small proportion of endothelial cells in both anterior and posterior lobes. Staining was also noted in several pituicytes, neurohypophysial nerve fibers, and Herring bodies. In contrast to CD-34 and Factor-8 immunostaining which demonstrated immunopositivity in practically all endothelial cells of every capillary, nestin expression was only focally seen suggesting that the functional status of the immunoreactive and non-staining endothelial cells was not the same. No statistically significant correlation was apparent between nestin immunoreactivity and patient age, gender, tumor size, mitotic index, Ki-67, labeling nuclear index, hormonal immunoprofile, and tumor type. In conclusion, nestin expression in adenomas cannot be viewed as a biologically relevant marker of cell proliferation and as a prognostic indicator. The patchy expression of nestin in endothelial cells remains unexplained and its significance requires further studies.

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References

  1. About I, Laurent-Maquin D, Lendahl U, Mitsiadis TA (2000) Nestin expression in embryonic and adult human teeth under normal and pathological conditions. Am J Pathol 157:287–295

    PubMed  CAS  Google Scholar 

  2. Aihara M, Sugawara K, Torii S, Hosaka M, Kurihara H, Saito N, Takeuchi T (2004) Angiogenic endothelium-specific nestin expression is enhanced by the first intron of the nestin gene. Lab Invest 84:1581–1592

    Article  PubMed  CAS  Google Scholar 

  3. Almqvist PM, Mah R, Lendahl U, Jacobsson B, Hendson G (2002) Immunohistochemical detection of nestin in pediatric brain tumors. J Histochem Cytochem 50:147–158

    PubMed  CAS  Google Scholar 

  4. Dahlstrand J, Collins VP, Lendahl U (1992) Expression of the class VI intermediate filament nestin in human central nervous system tumors. Cancer Res 52:5334–5341

    PubMed  CAS  Google Scholar 

  5. Dahlstrand J, Lardelli M, Lendahl U (1995) Nestin mRNA expression correlates with the central nervous system progenitor cell state in many, but not all, regions of developing central nervous system. Dev Brain Res 84:109–129

    Article  PubMed  CAS  Google Scholar 

  6. Davidoff MS, Middendorff R, Enikolopov G, Riethmacher D, Holstein AF, Muller D (2004) Progenitor cells of the testosterone-producing Leydig cells revealed. J Cell Biol 167:935–944

    Article  PubMed  CAS  Google Scholar 

  7. Duggal N, Iskander S, Hammond RR (2001) Nestin expression in cortical dysplasia. J Neurosurg 95:459–465

    Article  PubMed  CAS  Google Scholar 

  8. Frisen J, Johansson CB, Torok C, Risling M, Lendahl U (1995) Rapid, widespread, and long-lasting induction of nestin contributes to the generation of glial scar tissue after CNS injury. J Cell Biol 131:453–464

    Article  PubMed  CAS  Google Scholar 

  9. Ha Y, Kim TS, Yoon DH, Cho YE, Huh SG, Lee KC (2003) Reinduced expression of developmental proteins (nestin, small heat shock protein) in and around cerebral arteriovenous malformations. Clin Neuropathol 22:252–261

    PubMed  CAS  Google Scholar 

  10. Horvath E, Kovacs K (1998) The adenohypophysis. In: Kovacs K, Asa SL (eds) Functional endocrine pathology. Blackwell, Boston, pp 247–281

    Google Scholar 

  11. Horvath E, Scheithauer BW, Kovacs K, Lloyd RV (1997) Regional neuropathology: hypothalamus, pituitary. In: Graham DI, Lantos PL (eds) Greenfield’s neuropathology, 6th edn. Arnold, London, pp 1007–1094

    Google Scholar 

  12. Kachinsky AM, Dominov JA, Miller JB (1995) Intermediate filaments in cardiac myogenesis: nestin in the developing mouse heart. J Histochem Cytochem 43:843–847

    PubMed  CAS  Google Scholar 

  13. Kobayashi M, Sjoberg G, Soderhall S, Lendahl U, Sandstedt B, Sejersen T (1998) Pediatric rhabdomyosarcomas express the intermediate filament nestin. Pediatr Res 43:386–392

    Article  PubMed  CAS  Google Scholar 

  14. Kovacs K, Lloyd R, Horvath E et al (1989) Silent somatotroph adenomas of the human pituitary. A morphologic study of three cases including immunocytochemistry, electron microscopy, in vitro examination, and in situ hybridization. Am J Pathol 134:345–353

    PubMed  CAS  Google Scholar 

  15. Kovacs K, Stefaneanu L, Horvath E et al (1991) Effect of dopamine agonist medication on prolactin producing pituitary adenomas. A morphological study including immunocytochemistry, electron microscopy and in situ hybridization. Virchows Arch A Pathol Anat Histopathol 418:439–446

    Article  PubMed  CAS  Google Scholar 

  16. Krum JM, Rosenstein JM (1999) Transient co-expression of nestin, GFAP, and vascular endothelial growth factor in mature reactive astroglia following neural grafting or brain wounds. Exp Neurol 160:348–360

    Article  PubMed  CAS  Google Scholar 

  17. Krylyshkina O, Chen J, Mebis L, Denef C, Vankelecom H (2005) Nestin-immunoreactive cells in rat pituitary are neither hormonal nor typical folliculo-stellate cells. Endocrinology 146:2376–2387

    Article  PubMed  CAS  Google Scholar 

  18. Lendahl U, Zimmerman LB, McKay RD (1990) CNS stem cells express a new class of intermediate filament protein. Cell 60:585–595

    Article  PubMed  CAS  Google Scholar 

  19. Li Y, Chopp M (1999) Temporal profile of nestin expression after focal cerebral ischemia in adult rat. Brain Res 838:1–10

    Article  PubMed  CAS  Google Scholar 

  20. Lloyd RV, Scheithauer BW, Kuroki T, Vidal S, Kovacs K, Stefaneanu L (1999) Vascular endothelial growth factor (VEGF) expression in human pituitary adenomas and carcinomas. Endocr Pathol 10:229–235

    Article  PubMed  CAS  Google Scholar 

  21. Michalczyk K, Ziman M (2005) Nestin structure and predicted function in cellular cytoskeletal organization. Histol Histopathol 20:665–671

    PubMed  CAS  Google Scholar 

  22. Mokry J, Nemecek S (1999) Cerebral angiogenesis shows nestin expression in endothelial cells. Gen Physiol Biophys 18(Suppl 1):25–29

    PubMed  Google Scholar 

  23. Mokry J, Cizkova D, Filip S, Ehrmann J, Osterreicher J, Kolar Z, English D (2004) Nestin expression by newly formed human blood vessels. Stem Cells Dev 13:658–664

    Article  PubMed  CAS  Google Scholar 

  24. Nakagawa T, Miyamoto O, Janjua NA, Auer RN, Nagao S, Itano T (2004) Localization of nestin in amygdaloid kindled rat: an immunoelectron microscopic study. Can J Neurol Sci 31:514–519

    PubMed  Google Scholar 

  25. Niki T, Pekny M, Hellemans K et al (1999) Class VI intermediate filament protein nestin is induced during activation of rat hepatic stellate cells. Hepatology 29:520–527

    Article  PubMed  CAS  Google Scholar 

  26. Rotondo F, Vidal S, Bell D et al (2003) Immunohistochemical localization of amylin in human pancreas, thyroid, pituitary and their tumors. Acta Histochem 105:303–307

    Article  PubMed  Google Scholar 

  27. Rotondo F, Horvath E, Kovacs K, Bell DC, Lloyd RV, Scheithauer BW (2004) Expression of caveolin-1 and caveolin-2 in the human pituitary: an immunohistochemical study. Endocr Pathol 15:345–350

    Article  PubMed  Google Scholar 

  28. Rutka JT, Ivanchuk S, Mondal S et al (1999) Co-expression of nestin and vimentin intermediate filaments in invasive human astrocytoma cells. Int J Dev Neurosci 17:503–515

    Article  PubMed  CAS  Google Scholar 

  29. Sarlomo-Rikala M, Tsujimura T, Lendahl U, Miettinen M (2002) Patterns of nestin and other intermediate filament expression distinguish between gastrointestinal stromal tumors, leiomyomas and schwannomas. APMIS 110:499–507

    Article  PubMed  CAS  Google Scholar 

  30. Shibuya S, Miyamoto O, Auer RN, Itano T, Mori S, Norimatsu H (2002) Embryonic intermediate filament, nestin, expression following traumatic spinal cord injury in adult rats. Neuroscience 114:905–916

    PubMed  CAS  Google Scholar 

  31. Singh SK, Clarke ID, Hide T, Dirks PB (2004) Cancer stem cells in nervous system tumors. Oncogene 23:7267–7273

    Article  PubMed  CAS  Google Scholar 

  32. Sugawara K, Kurihara H, Negishi M et al (2002) Nestin as a marker for proliferative endothelium in gliomas. Lab Invest 82:345–351

    PubMed  CAS  Google Scholar 

  33. Thapar K, Kovacs K, Scheithauer BW et al (1996a) Proliferative activity and invasiveness among pituitary adenomas and carcinomas: an analysis using the MIB-1 antibody. Neurosurgery 38:99–106; discussion 106–107

    Article  CAS  Google Scholar 

  34. Thapar K, Yamada Y, Scheithauer B, Kovacs K, Yamada S, Stefaneanu L (1996b) Assessment of mitotic activity in pituitary adenomas and carcinomas. Endocr Pathol 7:215–221

    Article  Google Scholar 

  35. Tohyama T, Lee VM, Rorke LB, Marvin M, McKay RD, Trojanowski JQ (1992) Nestin expression in embryonic human neuroepithelium and in human neuroepithelial tumor cells. Lab Invest 66:303–313

    PubMed  CAS  Google Scholar 

  36. Tsujimura T, Makiishi-Shimobayashi C, Lundkvist J et al (2001) Expression of the intermediate filament nestin in gastrointestinal stromal tumors and interstitial cells of Cajal. Am J Pathol 158:817–823

    PubMed  CAS  Google Scholar 

  37. Umeoka S, Miyamoto O, Nakagawa T, Janjua NA, Nagao S, Itano T (2001) Expression of an embryonic intermediate filament protein in amygdaloid kindled rats. Epilepsy Res 43:249–253

    Article  PubMed  CAS  Google Scholar 

  38. Vanderwinden JM, Gillard K, De Laet MH, Messam CA, Schiffmann SN (2002) Distribution of the intermediate filament nestin in the muscularis propria of the human gastrointestinal tract. Cell Tissue Res 309:261–268

    Article  PubMed  CAS  Google Scholar 

  39. Vidal S, Kovacs K, Horvath E, Scheithauer BW, Kuroki T, Lloyd RV (2001) Microvessel density in pituitary adenomas and carcinomas. Virchows Arch 438:595–602

    Article  PubMed  CAS  Google Scholar 

  40. Zulewski H, Abraham EJ, Gerlach MJ et al (2001) Multipotential nestin-positive stem cells isolated from adult pancreatic islets differentiate ex vivo into pancreatic endocrine, exocrine, and hepatic phenotypes. Diabetes 50:521–533

    Article  PubMed  CAS  Google Scholar 

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Acknowledgement

Authors are indebted to The Jarislowsky Foundation and the Lloyd Carr-Harris Foundation for their support and Ms. Corinne Holubowich for the literature search.

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Correspondence to Fabio Rotondo.

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Rotondo, F., Kovacs, K., Horvath, E. et al. Immunohistochemical expression of nestin in the non-tumorous hypophysis and in pituitary neoplasms. Acta Neuropathol 111, 272–277 (2006). https://doi.org/10.1007/s00401-006-0031-6

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  • DOI: https://doi.org/10.1007/s00401-006-0031-6

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