Endocrine Pathology

, Volume 13, Issue 3, pp 197–206 | Cite as

Growth factors and cytokines in paragangliomas and pheochromocytomas, with special reference to sustentacular cells

  • George Kontogeorgos
  • Bernd W. Scheithauer
  • Kalman Kovacs
  • Eva Horvath
  • Shlomo Melmed
Clinical Research

Abstract

The aim of this study was to localize various growth factors and cytokines in paragangliomas and pheochromocytomas in order to understand their possible autocrine or paracrine functions, and to compare sustentacular cells of the adrenal medulla with pituitary stellate cells. Thirteen resected tumors, 11 paragangliomas and 2 pheochromocytomas of the adrenal medulla, were studied. In addition, five surgically removed nontumorous adrenals and five nontumorous pituitaries were studied. Varying numbers of sustentacular cells were immunopositive for S-100 protein and in most instances for glial fibrillary acidic protein. Insulin-like growth factor-1 (IGF-1), tumor necrosis factor-α (TNF-α), and interleukin-6 were localized to both cell types in all cases, whereas epidermal growth factor (EGF) immunopositivity was noted in only three. In all tumors, leukemia inhibitory factor (LIF) was restricted to chief cells and EGF receptor to sustentacular cells. Nontumorous chief cells and sustentacular cells of adrenal medulla exhibited immunoreactivities similar to those of paragangliomas and pheochromocytomas. Secretory adenohypophysial cells displayed various immunoreactivities for all growth factors, receptors, and cytokines studied. Pituitary stellate cells were immunopositive for EGF, EGF receptor, IGF-1, LIF, and TNF-α. In conclusion, paragangliomas and pheochromocytomas are immunoreactive for a wide spectrum of growth factors and cytokines. Immunocytochemistry demonstrated similarities between sustentacular cells and stellate cells of the pituitary in addition to their similar morphology. The significance of these observations regarding paracrine activities of chief and sustentacular cells remains to be determined.

Key Words

Growth factors cytokines immunocytochemistry paraganglioma pituitary gland stellate cells sustentacular cells 

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References

  1. 1.
    Glener GG, Grimely PM. Tumors of the extraadrenal paraganglion system (including chemoreceptors). In: Firminyer HI, ed. Atlas of pathology. 2nd series. Fascicle 9. Washington, DC: Armed Forces Institute of Pathology, 1974; 13–86.Google Scholar
  2. 2.
    Tischler AS. The adrenal medulla and extraadrenal paraganglia. In: Kovacs K, Asa SL, eds. Functional endocrine pathology. Boston, MA: Blackwell Scientific, 1998; 550–595.Google Scholar
  3. 3.
    Erlandson RA. Diagnostic transmission electron microscopy of tumors with clinicopathological, immunohistochemical, and cytogenetic correlations. New York, Raven, 1994; 615–622.Google Scholar
  4. 4.
    Johnson TL, Shapiro B, Beierwatles WH, Orringer MB, Lloyd RV, Sisson JC, Thompsom NW. Cardiac paragangliomas: a clinicopathologic and immunohistochemical study of four cases. Am J Surg Pathol 9:827–834, 1985.PubMedCrossRefGoogle Scholar
  5. 5.
    Kliewer KE, Wen D-R, Cancilla PA, Cochran AJ. Paragangliomas: assessment of prognosis by histology, immunohistochemical, and ultrastructural techniques. Hum Pathol 20:29–39, 1989.PubMedCrossRefGoogle Scholar
  6. 6.
    Lloyd RV, Blaivas M, Wilson BS. Distribution of chromogranin and S-100 protein in normal and abnormal adrenal medullary tissues. Arch Pathol Lab Med 109:633–635, 1985.PubMedGoogle Scholar
  7. 7.
    Nakajima T, Watanabe S, Sato Y, Kameya T, Hirota T, Shimosato Y. An immunoperoxidase study of S-100 protein distribution in normal and neoplastic tissues. Am J Surg Pathol 6:715–727, 1982.PubMedCrossRefGoogle Scholar
  8. 8.
    Perrone T, Sibley RK, Rossai J. Duodenal gangliocytic paraganglioma: an immunohistochemical and ultrastructural study and a hypothesis concerning its origin. Am J Surg Pathol 9:31–41, 1985.PubMedCrossRefGoogle Scholar
  9. 9.
    Vinores SA, Bonnin JM, Rubinstein LJ, Marangos PJ. Immunohistochemical demonstration of neuron-specific enolase in neoplasms of the CNS and other tissues. Arch Pathol Lab Med 108:536–540, 1984.PubMedGoogle Scholar
  10. 10.
    Assaf HM, Al-Momen AA, Martin JG. Aorticopulmonary paraganglioma: a case report with immunohistochemical studies and literature review. Arch Pathol Lab Med 116:1085–1087, 1991.Google Scholar
  11. 11.
    Hirose T, Sano T, Mori K, Kagawa N, Sakari A, Kuwamura Y, Hizawa K. Paraganglioma of the cauda equina: an ultrastructural and immunohistochemical study of two cases. Ultrastruct Pathol 12:235–243, 1988.PubMedGoogle Scholar
  12. 12.
    Korat O, LiVolsi VA, Trojanowski JQ, Merino MJ. Antigen expression in normal paraganglia and paragangliomas. Surg Pathol 1:33–40, 1988.Google Scholar
  13. 13.
    Sonneland PRL, Scheithauer BW, LeChago J, Crawford BG, Onofrio BM. Paraganglioma of the cauda equina region: clinicopathologic study of 31 cases with special reference to immunohistochemical and ultrastructural analysis. Cancer 58:385–391, 1986.CrossRefGoogle Scholar
  14. 14.
    Warren WH, Lee I, Gould VE, Memoli VA, Jao W. Paragangliomas of the head and neck: ultrastructural and immunohistochemical analysis. Ultrastruct Pathol 8:333–343, 1985.PubMedGoogle Scholar
  15. 15.
    Kliewer KE, Cochran AJ. A review of the histology, ultrastructure, immunohistology, and molecular biology of extra-adrenal paragangliomas. Arch Pathol Lab Med 113:1209–1218, 1989.PubMedGoogle Scholar
  16. 16.
    Marin F, Kovacs K, Stefaneanu L, Horvath E, Cheng Z. S-100 protein immunoreactivity in human nontumorous adenohypophyses and pituitary adenomas. Endocr Pathol 3:28–38, 1992.Google Scholar
  17. 17.
    Moris CS, Hitchkock E. Immunocytochemistry of folliculo-stellate cells of normal and neoplastic human pituitary gland. J Clin Pathol 38:481–488, 1985.Google Scholar
  18. 18.
    Akita S, Webster J, Ren SG, Takino H, Said J, Zand O, Melmed S. Human and murine pituitary expression of leukemia inhibitory factor: Novel intrapituitary regulation of adrenocorticotropin hormone synthesis and secretion. J Clin Invest 95:1288–1298, 1995.PubMedGoogle Scholar
  19. 19.
    Tsagarakis S, Kontogeorgos G, Giannou P, Thalassinos N, Besser GM, Grossman A. Interleukin-6, a growth promoting cytokine, is present in human pituitary adenomas: an immunocytochemical study. Clin Endocrinol 37:163–167, 1992.Google Scholar
  20. 20.
    Kontogeorgos G, Stefaneanu L, Kovacs K, Cheng Z. Localization of epidermal growth factor (EGF) and epidermal growth factor receptor (EGFr) in human pituitary adenomas and nontumorous pituitaries: an immunocytochemical study. Endocr Pathol 7:63–70, 1996.PubMedGoogle Scholar
  21. 21.
    Kontogeorgos G, Patralexis H, Tran A, Kovacs K, Melmed S. Expression of leukemia inhibitory factor in human pituitary adenomas: a morphologic study. Pituitary 2:245–251, 2000.PubMedCrossRefGoogle Scholar
  22. 22.
    Ferrara N, Henzel WJ. Pituitary follicular cells secrete a novel heparin-binding growth factor specific for vascular endothelial cells. Biochem Biophys Res Commun 161:851–858, 1989.PubMedCrossRefGoogle Scholar
  23. 23.
    Ray D, Melmed S. Pituitary cytokine and growth factor expression and action. Endocr Rev 18:206–228, 1997.PubMedCrossRefGoogle Scholar
  24. 24.
    Tsagarakis S, Kontogeorgos G, Kovacs K. The role of cytokines in the normal and neoplastic pituitary. Crit Rev Oncol/Hematol 28:73–90, 1998.CrossRefGoogle Scholar
  25. 25.
    Path G, Bornstein SR, Ehrhart-Bornstein M, Scherbaum WA. Interleukin-6 and the interleukin-6 receptor in the human adrenal gland: expression and effects on steroidogenesis. J Clin Endocrinol Metab 82:2343–2349, 1997.PubMedCrossRefGoogle Scholar
  26. 26.
    Nussdorfer GG, Mazzocchi G. Immune-endocrine interactions in the mammalian adrenal gland: facts and hypotheses. Int Rev Cytol 183:143–184, 1998.PubMedCrossRefGoogle Scholar
  27. 27.
    Nilsson O, Wängberg B, Kölby L, Schultz GS, Ahlman H. Expression of transforming growth factor alpha and its receptor in human neuroendocrine tumors. Int J Cancer 60:645–651, 1995.PubMedCrossRefGoogle Scholar
  28. 28.
    Kahn JH, Marks A, Thom H, Baumal R. Role of antibody to S-100 protein in diagnostic pathology. Am J Clin Pathol 79:341–347, 1983.PubMedGoogle Scholar
  29. 29.
    Gosney JR, Denley H, Resl M. Sustentacular cells in pulmonary neuroendocrine tumours. Histopathology 14:211–215, 1999.CrossRefGoogle Scholar
  30. 30.
    Hoefler H, Auboeck L. S-100 protein in carcinoiden. Ver Dtch Ges Path 68:86–91, 1984.Google Scholar
  31. 31.
    Lundqvist M, Wilander E. Superepithelial neuroendocrine cells and carcinoid tumours of the human intestine and appendix: a comparative immunohistochemical study with regard to serotonin, neuron-specific enolase and S-100 protein reactivity. J Pathol 148:141–147, 1986.PubMedCrossRefGoogle Scholar
  32. 32.
    Lloyd RV. Cytology and function of the pituitary gland. In: Lloyd RV, ed. Surgical pathology of the pituitary gland. Philadelphia: Saunders, 1993; 5–17.Google Scholar
  33. 33.
    Ferrara N, Schweigerer L, Neufeld G, Michell R, Gospodarowicz D. Pituitary follicular cells produce basic fibroblast growth factor. Proc Natl Acad Sci USA 84:5773–5777, 1987.PubMedCrossRefGoogle Scholar

Copyright information

© Humana Press Inc. 2002

Authors and Affiliations

  • George Kontogeorgos
    • 1
    • 4
  • Bernd W. Scheithauer
    • 2
  • Kalman Kovacs
    • 1
  • Eva Horvath
    • 1
  • Shlomo Melmed
    • 3
  1. 1.Department of Laboratory Medicine and PathologySt. Michael’s Hospital, University of TorontoTorontoCanada
  2. 2.Department of Laboratory Medicine and PathologyMayo ClinicRochester
  3. 3.Division of Endocrinology and MetabolismCedars Sinai Medical CenterLos Angeles
  4. 4.Department of PathologyGeneral Hospital of AthensAthensGreece

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