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. 1987 Sep;128(3):464–470.

Immunohistochemical Evidence of Active Thymocyte Proliferation in Thymoma

Its Possible Role in the Pathogenesis of Autoimmune Diseases

Marco Chilosi, Antonio Iannucci, Fabio Menestrina, Maurizio Lestani, Aldo Scarpa, Franco Bonetti, Luciano Fiore-Donati, Bruno Dipasquale, Giovanni Pizzolo, Giorgio Palestro, Giuseppe Tridente, George Janossy
PMCID: PMC1899674  PMID: 2443011

Abstract

Eight cases of human thymoma have been analyzed on cryostat sections with the monoclonal antibody Ki67, which reacts with cells in the proliferative phases of the cell cycle. The aim was to assess the proportion of proliferating thymocytes among lymphoid cells in the thymoma samples. In all cases a large number of cells (mean, 58.75%; range, 35-80%), recognized as thymocytes by morphology and lack of cytokeratin expression in a combined immunohistochemical assay, exhibited nuclear Ki67 staining. These findings differ from the reactivity pattern observed in age-matched nonneoplastic thymuses where lower growth activity of cortical thymocytes was observed (15-20% Ki67+ cells). Intensive thymocyte proliferation in thymomas may represent one of the factors which lead to autoimmunity in myasthenia gravis and thymomas.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aisenberg A. C., Wilkes B., Harris N. L., Frist W. H. The predominant lymphocyte in most thymomas and in nonneoplastic thymus from patients with myasthenia gravis is the cortical thymocyte. Clin Immunol Immunopathol. 1985 Apr;35(1):130–136. doi: 10.1016/0090-1229(85)90086-8. [DOI] [PubMed] [Google Scholar]
  2. Chan W. C., Zaatari G. S., Tabei S., Bibb M., Brynes R. K. Thymoma: an immunohistochemical study. Am J Clin Pathol. 1984 Aug;82(2):160–166. doi: 10.1093/ajcp/82.2.160. [DOI] [PubMed] [Google Scholar]
  3. Chilosi M., Iannucci A. M., Pizzolo G., Menestrina F., Fiore-Donati L., Janossy G. Immunohistochemical analysis of thymoma. Evidence for medullary origin of epithelial cells. Am J Surg Pathol. 1984 Apr;8(4):309–318. doi: 10.1097/00000478-198404000-00009. [DOI] [PubMed] [Google Scholar]
  4. Chilosi M., Iannucci A., Fiore-Donati L., Tridente G., Pampanin M., Pizzolo G., Ritter M., Bofill M., Janossy G. Myasthenia gravis: immunohistological heterogeneity in microenvironmental organization of hyperplastic and neoplastic thymuses suggesting different mechanisms of tolerance breakdown. J Neuroimmunol. 1986 May;11(3):191–204. doi: 10.1016/0165-5728(86)90003-2. [DOI] [PubMed] [Google Scholar]
  5. Chilosi M., Pizzolo G., Fiore-Donati L., Bofill M., Janossy G. Routine immunofluorescent and histochemical analysis of bone marrow involvement of lymphoma/leukaemia: the use of cryostat sections. Br J Cancer. 1983 Dec;48(6):763–775. doi: 10.1038/bjc.1983.265. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Cordell J. L., Falini B., Erber W. N., Ghosh A. K., Abdulaziz Z., MacDonald S., Pulford K. A., Stein H., Mason D. Y. Immunoenzymatic labeling of monoclonal antibodies using immune complexes of alkaline phosphatase and monoclonal anti-alkaline phosphatase (APAAP complexes). J Histochem Cytochem. 1984 Feb;32(2):219–229. doi: 10.1177/32.2.6198355. [DOI] [PubMed] [Google Scholar]
  7. Dalakas M. C., Engel W. K., McClure J. E., Goldstein A. L., Askanas V. Immunocytochemical localization of thymosin-alpha 1 in thymic epithelial cells of normal and myasthenia gravis patients and in thymic cultures. J Neurol Sci. 1981 May;50(2):239–247. doi: 10.1016/0022-510x(81)90170-2. [DOI] [PubMed] [Google Scholar]
  8. Eimoto T., Teshima K., Shirakusa T., Takeshita M., Okamura H., Naito H., Mitsui T., Kikuchi M. Heterogeneity of epithelial cells and reactive components in thymomas: an ultrastructural and immunohistochemical study. Ultrastruct Pathol. 1986;10(2):157–173. doi: 10.3109/01913128609014592. [DOI] [PubMed] [Google Scholar]
  9. Gerdes J., Lemke H., Baisch H., Wacker H. H., Schwab U., Stein H. Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol. 1984 Oct;133(4):1710–1715. [PubMed] [Google Scholar]
  10. Janossy G., Thomas J. A., Bollum F. J., Granger S., Pizzolo G., Bradstock K. F., Wong L., McMichael A., Ganeshaguru K., Hoffbrand A. V. The human thymic microenvironment: an immunohistologic study. J Immunol. 1980 Jul;125(1):202–212. [PubMed] [Google Scholar]
  11. Lauriola L., Maggiano N., Marino M., Carbone A., Piantelli M., Musiani P. Human thymoma: immunologic characteristics of the lymphocytic component. Cancer. 1981 Nov 1;48(9):1992–1995. doi: 10.1002/1097-0142(19811101)48:9<1992::aid-cncr2820480914>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  12. Levine G. D., Polliack A. The T-cell nature of the lymphocytes in two human epithelial thymomas: a comparative immunologic, scanning and transmission electron microscopic study. Clin Immunol Immunopathol. 1975 Jul;4(2):199–208. doi: 10.1016/0090-1229(75)90055-0. [DOI] [PubMed] [Google Scholar]
  13. Lo D., Sprent J. Identity of cells that imprint H-2-restricted T-cell specificity in the thymus. Nature. 1986 Feb 20;319(6055):672–675. doi: 10.1038/319672a0. [DOI] [PubMed] [Google Scholar]
  14. Matsui M., Kameyama M. A double-label flow cytometric analysis of the simultaneous expression of OKT4 and Leu2a antigens on circulating T lymphocytes in myasthenia gravis. J Neuroimmunol. 1986 Jun;11(4):311–319. doi: 10.1016/0165-5728(86)90084-6. [DOI] [PubMed] [Google Scholar]
  15. Musiani P., Maggiano N., Aiello F. B., Larocca L. M., Piantelli M. Phenotypical characteristics and proliferative capabilities of thymocyte subsets in human thymoma. Clin Immunol Immunopathol. 1986 Sep;40(3):385–392. doi: 10.1016/0090-1229(86)90182-0. [DOI] [PubMed] [Google Scholar]
  16. Müller-Hermelink H. K., Marino M., Palestro G. Pathology of thymic epithelial tumors. Curr Top Pathol. 1986;75:207–268. doi: 10.1007/978-3-642-82480-7_7. [DOI] [PubMed] [Google Scholar]
  17. Reddick R. L., Jennette J. C. Immunologic and ultrastructural characterization of the small cell population in malignant thymoma. Hum Pathol. 1983 Apr;14(4):377–380. doi: 10.1016/s0046-8177(83)80127-0. [DOI] [PubMed] [Google Scholar]
  18. Rosenow E. C., 3rd, Hurley B. T. Disorders of the thymus. A review. Arch Intern Med. 1984 Apr;144(4):763–770. [PubMed] [Google Scholar]
  19. Royer H. D., Acuto O., Fabbi M., Tizard R., Ramachandran K., Smart J. E., Reinherz E. L. Genes encoding the Ti beta subunit of the antigen/MHC receptor undergo rearrangement during intrathymic ontogeny prior to surface T3-Ti expression. Cell. 1984 Dec;39(2 Pt 1):261–266. doi: 10.1016/0092-8674(84)90003-5. [DOI] [PubMed] [Google Scholar]
  20. Schuurman H. J., van de Wijngaert F. P., Huber J., Schuurman R. K., Zegers B. J., Roord J. J., Kater L. The thymus in "bare lymphocyte" syndrome: significance of expression of major histocompatibility complex antigens on thymic epithelial cells in intrathymic T-cell maturation. Hum Immunol. 1985 Jun;13(2):69–82. doi: 10.1016/0198-8859(85)90014-x. [DOI] [PubMed] [Google Scholar]
  21. Snodgrass H. R., Kisielow P., Kiefer M., Steinmetz M., von Boehmer H. Ontogeny of the T-cell antigen receptor within the thymus. Nature. 1985 Feb 14;313(6003):592–595. doi: 10.1038/313592a0. [DOI] [PubMed] [Google Scholar]
  22. Souadjian J. V., Enriquez P., Silverstein M. N., Pépin J. M. The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med. 1974 Aug;134(2):374–379. [PubMed] [Google Scholar]
  23. Verley J. M., Hollmann K. H. Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. Cancer. 1985 Mar 1;55(5):1074–1086. doi: 10.1002/1097-0142(19850301)55:5<1074::aid-cncr2820550524>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  24. de Maagd R. A., MacKenzie W. A., Schuurman H. J., Ritter M. A., Price K. M., Broekhuizen R., Kater L. The human thymus microenvironment: heterogeneity detected by monoclonal anti-epithelial cell antibodies. Immunology. 1985 Apr;54(4):745–754. [PMC free article] [PubMed] [Google Scholar]

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