Skip to main content
SpringerLink
Log in

Proliferation markers and EGF in ACTH-secreting adenomas and carcinomas of the pituitary

  • Clinical Research
  • Published:
Endocrine Pathology Aims and scope Submit manuscript

Abstract

Pituitary carcinomas are only defined by their metastatic growth, which may be intracranial or systemic. To establish further morphological and immunohistochemical differences between pituitary carcinomas and adenomas, 19 ACTH-secreting adenomas (10 noninvasive and 9 invasive) and 2 ACTH-secreting carcinomas with their metastases were studied for expression of the intermediate filaments keratin and vimentin and the tumor-associated antigens Ki67, proliferating cell nuclear antigen (PCNA), epidermal growth factor (EGF), cathepsin D, p53, and carcinoembryonic antigen (CEA). Immunohistochemistry was performed using avidin-biotin techniques on formalin-fixed, paraffin-embedded tissue.

With the exception of one noninvasive pituitary adenoma, one carcinoma, and the metastases, all tumors contained keratin; none contained vimentin. All tumors stained negative for CEA and p53. Eleven (58.5%) adenomas and both pituitary carcinomas contained Ki67-positive nuclei; 14 (74%) adenomas and one carcinoma revealed PCNA. No correlation was found between the two markers. Seven (38%) adenomas showed a labeling index <1% for cathepsin D, whereas none of the carcinomas or metastases did so. EGF was found in 7 (38%) adenomas and in both carcinomas. A tendency to a higher rate of EGF positivity in the invasive adenomas was observed. The metastases showed a higher labeling index, and far more intense staining results for Ki67, PCNA, and EGF than the primary tumor The metastases also had a higher proliferation rate and growth factor content than the carcinoma itself.

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. Kovacs K, Horvath E, Asa SL. Classification and pathology of pituitary tumours. In: Wilkins RH, Rengachery S, eds. Neuro-oncology. New York: McGraw-Hill, 1985; 838.

    Google Scholar 

  2. Bailey OT, Cutler EC. Malignant adenoma of the chromophobe cells of the pituitary body. Arch Pathol 29: 368–399, 1940.

    Google Scholar 

  3. Jefferson G. Extrasellar extensions of pituitary adenomas. Proc R Soc Med 33: 433–458, 1940.

    Google Scholar 

  4. Kraus JE. Neoplastic disease of the human hypophysis. Arch Pathol 39: 343–349, 1945.

    Google Scholar 

  5. Newton TH, Burhenne HJ, Palubinskas J. Primary carcinoma of the pituitary. Am J Roentgenol 87: 110–119, 1962.

    CAS  Google Scholar 

  6. Scheithauer BW, Randall RV, Laws ER, Kovacs KT, Horvath E, Whitaker MD. Prolactin cell carcinoma of the pituitary. Cancer 55: 598–604, 1985.

    Article  PubMed  CAS  Google Scholar 

  7. Lubke, D. Zum Vergleich von Hypophysenadenomen und Hypophysencarzinomen. Eine immunhistologische Studie und Wertung der Literatur von 1904–1993. University of Hamburg, Thesis, 1994.

  8. Moll R, Franke WW, Schiller DL. The catalog of human cytokeratins: patterns of expression in normal ephithelia, tumours and cultured cells. Cell 31: 11–24, 1982.

    Article  PubMed  CAS  Google Scholar 

  9. Halliday WC, Kovacs K, Scheithauer BW. Intermediate filaments in the human pituitary gland: an immunohistochemical study. Can J Neurol Sci 17: 131–136, 1990.

    PubMed  CAS  Google Scholar 

  10. Höfler H, Denk H, Walter GF. Immunohistochemical demonstration of cytokeratins in endocrine cells of the human pituitary gland and in pituitary adenomas. Virchows Arch A Pathol Anat 404: 359–368, 1984.

    Article  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  12. Kasper M. Immunhistologische Untersuchungen zum Intermediarfilamentmuster der menschlichen Hypophyse und deren Adenome. Acta Histochem 42(Suppl): 221–223, 1992.

    CAS  Google Scholar 

  13. Ogawa A, Sugihara S, Hasegawa M, Sasaki A, Nakazato Y, Kawada T, Shogo I, Tamura M. Intermediate filament expression in pituitary adenomas. Virchows Arch B Cell Pathol 58: 341–349, 1990.

    CAS  Google Scholar 

  14. Lloyd J, McGuire JPW, Lee JCK. Coexpression of Cytokeratin and Vimentin. Appl Pathol 7: 73–84, 1989.

    Google Scholar 

  15. Kovacs K, Horvath E. Tumors of the pituitary gland. Atlas of tumor pathology. Sec Ser Fasc 21: 138–269, 1986.

    Google Scholar 

  16. Miyachi K, Fritzler MJ, Tan EM. Autoantibody to a nuclear antigen in proliferating cells. J Immunol 121: 2228–2234, 1978.

    PubMed  CAS  Google Scholar 

  17. Gerdes J, Schwab U, Lemke H, Stein H. Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31: 13–20, 1983.

    Article  PubMed  CAS  Google Scholar 

  18. Gerdes J, Lemke H, Baisch H, Wacker HH, Schwab U, Stein H. Cell cycle analysis of a cell proliferating-associated human nuclear antigen defined by the monoclonal antibody Ki67. J Immunol 133: 1710–1715, 1984.

    PubMed  CAS  Google Scholar 

  19. Celis JE, Madson P. Increased nuclear cyclin/ PCNA antigen staining of non S-phase transformed human amnion cells engaged in nucleotide excision DNA repair. FEBS Lett 209: 277–283, 1986.

    Article  PubMed  CAS  Google Scholar 

  20. Toschi L, Bravo R. Changes in cyclin/PCNA distribution during DNA repair synthesis. J Cell Biol 107: 1623–1628, 1988.

    Article  PubMed  CAS  Google Scholar 

  21. Kramer A, Saeger W, Tallen G, Ludecke DK. DNA measurement and proliferation markers in pituitary adenomas. Endocr Pathol (in press).

  22. Saeger W. Die Hypophysentumoren. Cytologische und ultrastrukturelle Klassifikation, Pathogenese, endokrine Funktionen und Tierexperiment. In: Bungeler W, Eder M, Lennert K, Peters G, Sandritta W, Seifert G, eds. Veröffentlichung aus der Pathologie, vol. 107. Stuttgart: G. Fischer, 1977; 1–240.

    Google Scholar 

  23. Brem S, Tsanaclis AMC, Gately S, Gross JL, Herblin WF. Immunolocalisation of basic fibroblast growth factor to the microvasculature of human brain tumors. Cancer 70: 2673–2680, 1992.

    Article  PubMed  CAS  Google Scholar 

  24. Burger PC, Shibata T, Kleihues P. The use of the monoclonal antibody Ki67 in identification of proliferating cells. Am J Surg Pathol 10: 611–617, 1986.

    Article  PubMed  CAS  Google Scholar 

  25. Hsu D, Hakim F, Biller BMK, De la Monte S, Zervas NT, Klibanski A, Hedley-Whyte ET. Significance of proliferating cell nuclear antigen index in predicting pituitary adenoma recurrence. J Neurosurg 78: 753–761, 1993.

    PubMed  CAS  Google Scholar 

  26. Knosp E, Kitz K, Perneczky A. Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki67. Neurosurgery 25: 927–930, 1989.

    Article  PubMed  CAS  Google Scholar 

  27. Landolt AM, Shibata T, Kleihues P. Growth rate of human pituitary adenomas. J Neurosurg 67: 803, 1989.

    Google Scholar 

  28. McNicol AM, Shepherd M, Lane DP. Cell proliferation in pituitary adenomas: correlation with hormonal immunoreactivity. J Endocrinol Invest 14: 55, 1991.

    Google Scholar 

  29. Shibuya M, Saito F, Miwa T, Davis RL, Wilson CB, Hoshino T. Histochemical study of pituitary adenomas with Ki67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts. Acta Neuropathol 84:178–183, 1992.

    Article  PubMed  CAS  Google Scholar 

  30. Tsanaclis AM, Robert F, Michaud J, Brem S. The cycling pool of cells within human brain tumours: in situ cytokinetics using the mono- clonal antibody Ki67. Can J Neurol Sci 18: 12–17, 1991.

    PubMed  CAS  Google Scholar 

  31. Mccormick D, Chong H, Hobbs C, Datta C, Hall PA. Detection of the Ki67 antigen in fixed and wax-embedded sections. Histopathology 22: 355–360, 1993.

    Article  PubMed  CAS  Google Scholar 

  32. Munakata S, Hendricks JB. Effect of fixation time and microwave oven heating time on retrieval of the KI-67 antigen from paraffinembedded tissue. J Histochem Cytochem 41: 1241–1246, 1993.

    PubMed  CAS  Google Scholar 

  33. Khazaie K, Schirrmacher V, Lichtner RB. EGF receptor in neoplasia and metastasis. Cancer Metastasis Rev 12, 3–4: 255-274, 1993.

    Article  Google Scholar 

  34. Halper J, Parnell PG, Carter BJ, Ren P, Scheithauer BW. Presence of growth factors in human pituitary. Lab Invest 66: 639, 1992.

    PubMed  CAS  Google Scholar 

  35. Kasselberg AG, Orth DN, Gray ME, Stahlman MT. Immunocytochemical localisation of human epidermal growth factor/Urogastrone in several human tissues. J Histochem Cytochem 33: 315–322, 1985.

    PubMed  CAS  Google Scholar 

  36. Ren P, Scheithauer BW, Halper J. Immunohistological localization of TGF alpha, EGF, IGF-I and TGF beta in the normal human pituitary gland. Endocr Pathol 5: 40–48, 1994.

    Article  Google Scholar 

  37. Hurliman J, Gebhard S, Gomez F. Estrogen receptor, progesterone receptor; Ps2, ERD5, HSP27 and Cathepsin D in invasive ductal breast carcinomas. Histopathology 23: 239–248, 1993.

    Article  Google Scholar 

  38. Marsigliante S, Leo G, Mottaghi A, Biscozzo L, Greco S, Storelli C. p53 associated with cathepsin D in primary breast cancer. Int J Clin Lab Res 23:102–108, 1993.

    Article  PubMed  CAS  Google Scholar 

  39. Tetu B, Brisson J, Cote C, Brisson S, Potvin D, Roberge N. Prognostic significance of Cathepsin D expression in node-positive breast carcinoma/3-an immunohistochemical study. Int J Cancer 55: 429–435, 1993.

    Article  PubMed  CAS  Google Scholar 

  40. Veneroni S, Daidone MG, Difronzo G, Cappelletti V, Amadori D, Riccobon A, Paradiso A, Correale M, Silvestrini R. Quantitative immunohistochemical determination of Cathepsin D and its relation with other variables. Breast Cancer Res Treatment 26: 7–13, 1993.

    Article  CAS  Google Scholar 

  41. Briozzo P, Morisset M, Capony F, Rougeot C, Rochefort H. In vitro degradation of extracellular matrix with Mr 52,000 Cathepsin D secreted by breast cancer cells. Cancer Res 48: 3688–3692, 1988.

    PubMed  CAS  Google Scholar 

  42. Charpin C, Devictor B, Bonnier P, Andrac L, Lavaut MN, Allasia C, Piana L. Cathepsin D immunocytochemical assays in breast carcinomas: image analysis and correlation to prognostic factors. J Pathol 170: 463–470, 1993.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Pathology of the Marienkrankenhaus Hamburg, Germany

    Dorothee Lübke & Wolfgang Saeger

  2. Department of Neurosurgery of the University of Hamburg, Germany

    Dieter K. Lüdecke

Authors
  1. Dorothee Lübke
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wolfgang Saeger
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Dieter K. Lüdecke
    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

Lübke, D., Saeger, W. & Lüdecke, D.K. Proliferation markers and EGF in ACTH-secreting adenomas and carcinomas of the pituitary. Endocr Pathol 6, 45–55 (1995). https://doi.org/10.1007/BF02914988

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF02914988

Key Words

Search

Navigation