Skip to main content
SpringerLink
Log in

Cytokeratin distribution and functional properties of growth hormone-producing pituitary adenomas

  • Original Article
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

In addition to its structural function, cytokeratin may have other important roles within cells. We have reported that in growth hormone-producing adenomas (GH cell adenomas), two distinct types can be recognized by their cytokeratin distribution patterns (dot-like or perinuclear pattern) and that each type has different clinicopathological and endocrinological properties. To confirm these phenomena in a larger series and to clarify the significance of different cytokeratin distribution patterns, we studied cytokeratin localization in 70 GH cell adenomas from acromegalic patients. Type I adenomas ( 15) almost exclusively (>98%) composed of cells with a prominent, dot-like distribution; type 2 adenomas (36) comprised of cells with perinuclear cytokeratin; and type 3 adenomas (11) comprised of both cell types were separated. The remaining 8 did not exhibit a distinct distribution pattern. By electron microscopic immunocytochemistry for cytokeratin, dot-like distribution corresponded to fibrous bodies, whereas perinuclear distribution represented immune deposition in the perinuclear zone. Immunohistochemistry for GH, prolactin, β-thyrotropin, and α-subunit of glycoprotein hormones revealed a reduced expression of these hormones in type 1 adenomas, compared with types 2 and 3 adenomas. In normal pituitary glands, almost all GH cells showed a perinuclear cytokeratin distribution, and only a few GH cells exhibited a dot-like pattern. These findings suggest that a dot-like cytokeratin distribution in GH cells may be pathological (a change from physiological perinuclear distribution) and that adenomas with such a distribution may reduce endocrine activities as a result of unknown factors.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Bando H, Sano T, Ohshima T, Zhang CY, Yamasaki R, Matsumoto K, Saito S. Differences in pathological findings and growth hormone responses in patients with growth hormone-producing pituitary adenoma. Endocrinol Jpn 39:355–363, 1992.

    Article  CAS  Google Scholar 

  2. Blose ST, Meltzer DI, Feramisco JR. 10-nm filaments are induced to collapse in living cells microinjected with monoclonal and polyclonal antibodies against tubulin. J Cell Biol 98:847–858, 1984.

    Article  CAS  Google Scholar 

  3. Doorbar J, Ely S, Sterling J, McLean C, Crawford L. Specific interaction between HPV-16 E1-E4 and cytokeratins results in collapse of the epithelial cell intermediate filament network. Nature 352:824–827, 1991.

    Article  CAS  Google Scholar 

  4. Fanghanel G, Larraza O, Villalobos M, Fanghanel L, Velasco M, Velasco F. Differential response to aminergic stimuli and biological behavior of growth hormone secreting pituitary adenomas. Can J Neurol Sci 17:78–82, 1990.

    Article  CAS  Google Scholar 

  5. Hüfler H, Denk H, Walter GF. Immuno- histochemical demonstration of cytokeratins in endocrine cells of the human pituitary gland and in pituitary adenomas. Virchows Arch [A] 404:359–368, 1984.

    Article  Google Scholar 

  6. Horvath E, Kovacs K. Morphogenesis and significance of fibrous bodies in human pituitary adenomas. Virchows Arch [B] 27:69–78, 1978.

    CAS  Google Scholar 

  7. Horvath E, Kovacs K. Fine structural cytology of the adenohypophysis in rat and man. J Electron Microsc Tech 8:401–432, 1988.

    Article  CAS  Google Scholar 

  8. Ironside JW, Royds JA, Jefferson AA, Timperley WR. Immunolocalisation of cytokeratins in the normal and neoplastic human pituitary gland. J Neurol Neurosurg Psychiatry 50:57–65, 1987.

    Article  CAS  Google Scholar 

  9. Ito K, Osamura Y. Immunohistochemical appearance of “keratin bodies” in the human pituitary GH producing adenomas and their clinicopathological significance. Pathol Clin 8:1175–1181, 1990 (in Japanese).

    Google Scholar 

  10. Kasper M, Stosiek P, van Muijen GNP, Moll R. Cell type heterogeneity of intermediate filament expression in epithelia of the human pituitary gland. Histochemistry 93: 93–103, 1989.

    Article  CAS  Google Scholar 

  11. Klymkowsky MW, Miller RH, Lane EB. Morphology, behavior, and interaction of cultured epithelial cells after the antibody-induced disruption of keratin filament organization. J Cell Biol 96:494–509, 1983.

    Article  CAS  Google Scholar 

  12. Knapp LW, O’Guin WM, Sawyer RH. Rearrangement of the keratin cytoskeleton after combined treatment with microtubule and microfilament inhibitors. J Cell Biol 97:1788–1794, 1983.

    Article  CAS  Google Scholar 

  13. Kovacs K, Horvath E. Pathology of growth hormone-producing tumors of the human pituitary. Semin Diagn Pathol 3:18–33, 1986.

    PubMed  CAS  Google Scholar 

  14. Melmed S. Acromegaly. N Engl J Med 322:966–977, 1990.

    Article  CAS  Google Scholar 

  15. Neumann PE, Goldman JE, Horoupian DS, Hess MA. Fibrous bodies in growth hormone-secreting adenomas contain cytokeratin filaments. Arch Pathol Lab Med 109:505–508, 1985.

    PubMed  CAS  Google Scholar 

  16. Riedel M, Saeger W, Ludecke DK. Grading of pituitary adenomas in acromegaly. Comparison of light microscopical, immunocytochemical, and clinical data. Virchows Arch [A] 407:83–95, 1985.

    Article  CAS  Google Scholar 

  17. Roy S. Cytoplasmic filamentous masses in chromophobe adenoma of the human pituitary gland. J Pathol 125:151–154, 1978.

    Article  CAS  Google Scholar 

  18. Sano T, Ohshima T, Yamada S. Expression of glycoprotein hormones and intracy toplasmic distribution of cytokeratin in growth hormone-producing pituitary adenomas. Pathol Res Pract 187:530–533, 1991.

    Article  CAS  Google Scholar 

  19. Sano T. Use of ultrastructural immuno-histochemistry in human pituitary pathology. Microsc Res Tech 20:152–161, 1992.

    Article  CAS  Google Scholar 

  20. Scheithauer BW, Horvath E, Kovacs K, Laws ER Jr, Randall RV, Ryan N. Plurihormonal pituitary adenomas. Semin Diagn Pathol 3:69–82, 1986.

    PubMed  CAS  Google Scholar 

  21. Shyy TT, Asch BB, Asch HL. Concurrent collapse of keratin filaments, aggregation of organelles, and inhibition of protein synthesis during the heat shock response in mammary epithelial cells. J Cell Biol 108:997–1008, 1989.

    Article  CAS  Google Scholar 

  22. Smedts F, Ramaekers F, Robben H, Pruszczynski M, van Muijen G, Lane B, Leigh I, Vooijs P. Changing patterns of keratin expression during progression of cervical intraepithelial neoplasia. Am J Pathol 136:657–668, 1990.

    PubMed  PubMed Central  CAS  Google Scholar 

  23. Trouillas J, Girod C, Lheritier M, Claustrat B, Dubois MP. Morphological and biochemical relationships in 31 human pituitary adenomas with acromegaly. Virchows Arch [A] 389:127–142, 1980.

    Article  CAS  Google Scholar 

  24. Trouillas J, Girod C, Loras B, Claustrat B, Sassolas G, Perrin G, Buonaguidi R. The TSH secretion in the human pituitary adenomas. Pathol Res Pract 183:596–600, 1988.

    Article  CAS  Google Scholar 

  25. Tsuneyoshi M, Daimaru Y, Hashimoto H, Enjoji M. The existance of rhabdoid cells in specified soft tissue sarcomas. Histopathological, ultrastructural and immunohistochemical evidence. Virchows Arch [A] 411:509–514, 1987.

    Article  CAS  Google Scholar 

  26. Weeks DA, Beckwith JB, Mierau GW, Zuppan CW. Renal neoplasms mimicking rhabdoid tumor of kidney. A report from the National Wilms’ Tumor Study Pathology Center. Am J Pathol 15:1042–1054, 1991.

    Article  CAS  Google Scholar 

  27. Yamada S, Sano T, Stefaneanu L, Kovacs K, Aiba T, Shishiba Y. Endocrine and morphologic study of a clinically silent somatotroph adenoma of the human pituitary. J Clin Endocrinol Metab 76:352–356, 1993.

    PubMed  CAS  Google Scholar 

  28. Yamada S, Takahashi M, Hara M, Sano T, Aiba T, Shishiba Y. GH and PRL gene expression in human densely granulated and sparsely granulated somatotroph adenomas using in situ hybridization with digoxigenin-labeled probes. Proceedings of 73th Endocrine Society Meeting, Las Vegas, Nevada, 1993 (abstract).

  29. Yamada S, Aiba T, Sano T, Kovacs K, Shishiba Y, Takada K. Gh-producing pituitary adenomas: Correlations between clinical or endocrinological findings and morphology. Neurosurgery 1994 (in press).

  30. Young DG, Bahn RC, Randall RV. Pituitary tumors associated with acromegaly. J Clin Endocr 25:249–259, 1965.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology, University of Tokushima School of Medicine, Tokushima

    Toshiaki Sano, Takashi Hi rose & Kazuo Hizawa

  2. Department of Neurosurgery, Toranomon Hospital, Tokyo, Japan

    Shozo Yamada

Authors
  1. Toshiaki Sano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Shozo Yamada
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Takashi Hi rose
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Kazuo Hizawa
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Sano, T., Yamada, S., Hi rose, T. et al. Cytokeratin distribution and functional properties of growth hormone-producing pituitary adenomas. Endocr Pathol 5, 107–113 (1994). https://doi.org/10.1007/BF02921378

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02921378

Keywords

Search

Navigation