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Proliferation Markers in Different Types of Clinically Non-Secreting Pituitary Adenomas

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Abstract

160 clinically non-secreting pituitary adenomas were examined in regard to their expression of the markers PCNA, bcl2, Ki 67 in the mib-1 modification and p53 which are still under investigation for their relevance to cell proliferation. The series contained 60 null cell adenomas, 60 oncocytomas and 40 gonadotroph adenomas. The groups that showed a definitely negative and definitely positive staining were evaluated in regard to their further characteristics such as size, invasiveness and recurrence. PCNA showed a highly represented immunostaining index throughout the groups, but not correlation between the PCNA index and an increased recurrence rate could be found. The staining for bcl2 was only rarely positive and only in a small number of cells. No correlation with the clinical data could be seen. We found a significant higher rate of staining in the invasive adenomas in the group of null cell adenomas and oncocytomas for Ki 67, especially in those adenomas expressing p53. p53 positivity was restricted to the invasive adenomas but was found only in 20% of all invasive adenomas. These data confirm in a sufficiently large series of clinically endocrine inactive pituitary adenomas, that p53 and Ki 67 immunohistology is usefull in evaluating the aggressive behavior of clinically silent pituitary adenomas. Nevertheless, negative results do not exclude clinically relevant invasive behavior.

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References

  1. Alvaro V, Levy L, Dubray C, Roche A, Peillon F, Querat B, Joubert D. Invasive human pituitary tumors express a point-mutated alpha-protein kinase-C. J Clin Endocrinol Metab 1993;77:1125–1129.

    Google Scholar 

  2. Asa SL, Kovacs K. Clinically non-functioning human pituitary adenomas. Can J Neurol Sci 1992;19:228–235.

    Google Scholar 

  3. Barbareschi M, Iuzzolino P, Penella A, Allegranza A, dalla Palma P, Doglioni C. p53 protein expression in central nervous system neoplasms. J Clin Pathol 1992;45:583–586.

    Google Scholar 

  4. Bourhis T, Bosq J, Wilson GD, Bressac B, Talbot M, Leridant AM, Dendale R, Janin N, Armand JP, Luboinski B, Malaise EP, Wibault P, Eshwege F. Correlation between p53 gene expression and tumor-cell proliferation in oropharyngeal cancer. Int J Cancer 1994;57:458–462.

    Google Scholar 

  5. Brown DC, Gatter KC. Monoclonal antibody Ki 67: Its use in histopathology. Histopathology 1990;17:489–503.

    Google Scholar 

  6. Buckley N, Bates AS, Broome J, Strange R, Perrett C, Burke C, Clayton R. p53 protein accumulates in Cushing' adenomas and invasive non-functional adenomas. J Clin Endocrinol Metab 1994;79:1513–1516.

    Google Scholar 

  7. Carbone DP, Mitsudomi T, Chiba I, Piantadoci S, Rusch V, Nowak JA, Mc Intire D, Slimon D, Gazdar A, Minna J. p53 immunostaining is associated with reduced survival and is imperfectly correlated with gene mutations in resected nonsmall cell lung cancer: A preliminary report of the LCSG 871. Chest 1994;106:377–381.

    Google Scholar 

  8. Gandour-Edwards R, Kapadia SB, Janecka I, Martinez AJ, Barnes L. Biologicalmarkers of invasive pituitary adenomas involving the sphenoid sinus. Modern Pathol 1995;8:160–164.

    Google Scholar 

  9. Gelsleichter L, Gown A, Zarbo R, Wang E, Coltrera M. p53 and mdm-2 expression in malignant melanoma: An immunhistochemical study of expression of p53, mdm-2 and markers of cell proliferation in primary versus metastatic tumors. Modern Pathol 1995;8:530–535.

    Google Scholar 

  10. Harris C, Hollstein M. Clinical implications of the p53 tumor suppressor gene. N Engl J Med 1993;329:1318–1327.

    Google Scholar 

  11. Holm R. Null cell adenomas and onocytomas of the pituitary gland. Path Res Pract 1995;191:348–352.

    Google Scholar 

  12. Hopf NJ, Brem J, Perneczky A. Image analysis of proliferating cells in tumors of the human nervous system: An immunohistochemical study with the monoclonal antibody Ki-67. Neurosurgery 1994;35:917–923.

    Google Scholar 

  13. Hsu DW, 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 1993;78:753–761.

    Google Scholar 

  14. Jensen RA, Page DI. p53: The promising story continues to unfold. Hum Pathol 1993;24:455–456.

    Google Scholar 

  15. Kawamato H, Uozumi T, Arita K, Yano T, Hirohata T. Analysis of the growth rate and cavernous sinus invasion of pituitary adenomas. Acta Neurochir 1995;136:37–43.

    Google Scholar 

  16. Kitz K, Knosp E, Koos WT, Korn A. Proliferation in pituitary adenomas: Measurement by MAb Ki-67. Acta Neurochir 1991;53:60–64.

    Google Scholar 

  17. Klibanski A. Nonsecreting pituitary tumors. J Clin Endocrinol Metab 1987;16:793–804.

    Google Scholar 

  18. Knosp E, Kitz K, Perneczky A. Proliferation activity in pi-tuitary adenomas:Measurement bymonoclonal antibody Ki-67. Neurosurgery 1989;25:927–930.

    Google Scholar 

  19. Landoldt A, Shibata T, Kleihues P. Growth rate of human pituitary adenomas. J Neurosurg 1987;67:803–806.

    Google Scholar 

  20. Landolt AM, Shibata T, Kleihues P, Tuncdogan E. Growth of human pituitary adenomas: Facts and speculations. Advances in the Biosciences 1988;69:53–62.

    Google Scholar 

  21. Levine AJ, Chang A, Dittmer D, Notterman DA, Silver A, Thorn K, Welsh D, Wu M. The p53 tumor suppressor gene. J Lab Clin Med 1994;123:817–823.

    Google Scholar 

  22. Levine AJ, Perry ME, Chang A, Silver D, Dittmer D, Wu M, Welsh D. The 1993 Walter Hubert Lecture: The role of the p53 tumor-suppressor gene in tumorigenesis. Br J Cancer 1994;69:409–416.

    Google Scholar 

  23. Levine AJ, Momand J, Finlay CA. The p53 tumor suppressor gene. Nature 1991;351:453–456.

    Google Scholar 

  24. Lüdecke DK, Beck-Bornholdt H-P, Saeger W, Schmidt W. Tumour ploidy in DNA histograms of pituitary adenomas. Acta Neurochir 1985;76:18–22.

    Google Scholar 

  25. Pernicone P, Scheithauer BW, Sebo T, Kovacs K, Horvath E, Young WF Jr, Ebersold MJ. Pituitary carcinoma: A clinicopathologic study of fifteen cases. J Neuropathol Exp Neurol 1995;54:456.

    Google Scholar 

  26. Sano T, Yamada S. Histologic and immunohistochemical study of clinically non-functioning pituitary adenomas: Special references to gonadotropin-positive adenomas. Pathol Int 1994;44:697–703.

    Google Scholar 

  27. Sautner D, Saeger W. Invasiveness of pituitary adenomas. Pathol Res Pract 1991;187:632–636.

    Google Scholar 

  28. Scheithauer BW, Kovacs KT, Laws ER, Randall RV. Pathology of pituitary tumors with special reference to functional classification. J Neurosurg 1986;65:733–744.

    Google Scholar 

  29. Shibuya M, Saito F, Miwa T, Davis RL, Wilson CB, Hoshino T. Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase alpha monoclonal antibodies, bromodeoxyuridine labeling and nucleolar organizer region counts. Acta Neuropathol 1992;84:178–183.

    Google Scholar 

  30. Sumi T, Stefaneanu L, Kovacs K, Asa S, Rindi G. Immunohistochemical study of p53 protein in human and animal pituitary tumors. Endocr Pathol 1993;4:95–99.

    Google Scholar 

  31. Thapar K, Kovacs K, Scheithauer BW, Stefaneanu L, Horvath E, Pernicone PJ, Murray D, Laws ER. Proliferative activity and invasiveness among pituitary adenomas and carcinomas: An analysis using the mib-1 antibody. Neurosurgery 1996;38:99–107.

    Google Scholar 

  32. Thapar K, Scheithauer BW, Kovacs K, Penicone PJ, Laws ER. p53 expression in pituitary adenomas and carcinomas: correlation with invasiveness and tumor growth fractions. Neurosurgery 1996;38:765–771.

    Google Scholar 

  33. Tsuzuki T, Tsunoda S, Sakaki T, Konoshi N, Hiasa Y, Nakamura M, Yoshino E. tumor cell proliferation and apoptosis associated with the gamma knife effect. Stereotact Funct Neurosurg 1996;66(suppl 1):39–48.

    Google Scholar 

  34. Wang D-C, Johnston CF, Atkinson AB, Heaney AP, Mirakhur M, Buchanan KD. Expression of bcl-2 oncoprotein in pituitary tumours: comparison with c-myc. J Clin Pathol 1996;49:795–797.

    Google Scholar 

  35. Yamada S, Asa SL, Kovacs K. Oncocytomas and null cell adenomas of the human pituitary: Morphometric and in vitro fuctional comparison. Virchows Archiv A Pathol Anat 1988; 413:333–339.

    Google Scholar 

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Authors and Affiliations

  1. Institute of Pathology of the Marienkrankenhaus, Hamburg, Germany

    Silke Schreiber & Wolfgang Saeger

  2. Clinic of Neurosurgery, University Hospital Eppendorf, Hamburg, Germany

    Dieter K. Lüdecke

Authors
  1. Silke Schreiber
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  2. Wolfgang Saeger
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  3. Dieter K. Lüdecke
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Schreiber, S., Saeger, W. & Lüdecke, D.K. Proliferation Markers in Different Types of Clinically Non-Secreting Pituitary Adenomas. Pituitary 1, 213–220 (1999). https://doi.org/10.1023/A:1009933820856

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