Summary
The growth potential of 65 pituitary adenomas was determined by histochemical analysis with Ki-67 and anti-DNA polymerase α monoclonal antibodies, bromodeoxyuridine (BrdUdR) labeling, and counts of argyrophilic nucleolar organizer regions (Ag-NORs). The mean proliferating cell indices (PCIs) determined by Ki-67 and anti-DNA polymerase α and the BrdUdR labeling index (LI) were generally very low [1.0±0.2%, 1.1±0.2%, and 0.5±0.1% (±SE), respectively]. Apart from adrenocorticotropic hormone-positive adenomas, which had significantly higher indices, there were no statistically significant differences in the indices among the other subtypes of pituitary adenomas. Recurrent tumors had higher Ki-67 and DNA polymerase α PCIs and BrdUdR LIs (3.6%, 4.2%, 1.4%) than primary tumors (0.8%, 0.8%, 0.3%; P<0.005). The number of Ag-NORs did not correlated significantly with any of the three indices. The mean number of Ag-NORs was higher in nonfunctioning adenomas than in functioning adenomas (2.04 vs 1.66, P<0.005); among prolactin-positive adenomas, those treated preoperatively with bromocriptine had more Ag-NORs than untreated tumors (1.75 vs 1.57, P<0.005). These results suggest that the Ki-67 and DNA polymerase α PCIs and the BrdUdR LI predict the growth potential of individual pituitary adenomas, whereas the number of Ag-NORs appears to correlate with hormone production rather than with the proliferative potential.
Article PDF
Similar content being viewed by others
Avoid common mistakes on your manuscript.
References
Anniko M, Holm L-E, Wersäll J (1983) Aggressive pituitary tumor growth. Arch Otorhinolaryngol 238:53–62
Asai A, Matsutani M, Funada N, Takakura K (1988) Malignant growth hormone-positive pituitary adenoma with hematogeneous dural metastasis: case report. Neurosurgery 22:1091–1094
Chun M, Masko GB, Hetelekidis S (1988) Radiotherapy in the treatment of pituitary adenomas. Int J Radiat Oncol Biol Phys 15:305–309
Crocker J, Nar P (1987) Nucleolar organizer regions in lymphomas. J Pathol 151:111–118
Gerdes J, Schwab U, Lemke H, Stein H (1983) Production of a mouse monoclonal antibody reactive with a human nuclear antigen associated with cell proliferation. Int J Cancer 31:13–20
Gerdes J, Lemke H, Baisch H, Wacker H-H, Schwab U, Stein H (1984) Cell cycle analysis of a cell proliferation-associated human nuclear antigen defined by the monoclonal antibody Ki-67. J Immunol 133:1710–1715
Giri DD, Nottingham JF, Lawry J, Dundas SAC, Underwood JCE (1989) Silver-binding nucleolar organizer regions (Ag-NORs) in benign and malignant breast lesions: correlations with ploidy and growth phase by DNA flow cytometry. J Pathol 157:307–313
Hall PA, Crocker J, Watts A, Stansfeld AG (1988) A comparison of nucleolar organizer region staining and Ki-67 immunostaining in non-Hodgkin's lymphoma. Histopathology 12:373–381
Horvath E, Kovacs K, Killinger DW, Smyth HS, Platts ME, Singer W (1980) Silent corticotropic adenomas of the human pituitary gland. A histologic, immunocytologic and ultrastructural study. Am J Pathol 98:617–638
Hoshino T, Nagashima T, Murovic JA, Wilson CB, Edwards MSB, Gutin PH, Davis RL (1986) In situ cell kinetics studies on human neuroectodermal tumors with bromodeoxyuridine labeling. J Neurosurg 64:453–459
Hoshino T, Prados M, Wilson CB, Cho KG, Lee K-S, Davis RL (1989) Prognostic implications of the bromodeoxyuridine labeling index of human gliomas. J Neurosurg 71:335–341
Johansen PW, Clausen OPF, Haug E, Fossum S, Gautvik KM (1985) Effects of bromocriptine on cell cycle distribution and cell morphology in cultured rat pituitary adenoma cells. Acta Endocrinol (Copenh) 110:319–328
Johansen PW, Haug E, Gautvik KM (1985) Effects of bromocriptine on hormone production and cell growth in cultured rat pituitary cells. Acta Endocrinol (Copenh) 110:200–206
Kajiwara K, Nishizaki T, Orita T, Nakayama H, Aoki H, Ito H (1990) Silver colloid staining technique for analysis of glioma malignancy. J Neurosurg 73:113–117
Knosp E, Kitz K, Perneczky A (1989) Proliferation activity in pituitary adenomas: measurement by monoclonal antibody Ki-67. Neurosurgery 25:927–930
Kunishio K, Mishima N, Matsuhisa T, Tsuno K, Matsumi N, Satoh T, Matsumoto K, Furuta T, Nishimoto A, Shiraishi T (1990) Immunohistochemical demonstration of DNA polymerase α in human brain-tumor cells. J Neurosurg 72:268–272
Landolt AM, Shibata T, Kleihues P (1987) Growth rate of human pituitary adenomas. J Neurosurg 67:803–806
Maier H, Morimura T, Öfner D, Hallbrucker C, Kitz K, Budka H (1990) Argyrophilic nucleolar organizer region proteins (Ag-NORs) in human brain tumors: relations with grade of malignancy and proliferation indices. Acta Neuropathol 80:156–162
Masaki S, Shiku H, Kaneda T, Koiwai O, Yoshida S (1982) Production and characterization of monoclonal antibody against 10S polymerase α from calf thymus. Nucleic Acids Res 10:4703–4713
McNicol AM, Colgan J, McMeekin W, Teasdale GM (1989) Nuclear organiser regions in pituitary adenomas. Acta Neuropathol 77:547–549
Nagashima T, Murovic JA, Hoshino T, Wilson CB, DeArmond SJ (1986) The proliferative potential of human pituitary tumors in situ. J Neurosurg 64:588–593
Nakamura H, Morita T, Masaki S, Yoshida S (1984) Intracellular localization and metabolism of DNA polymerase α in human cells visualized with monoclonal antibody. Exp Cell Res 151:123–133
Orita T, Kajiwara K, Nishizaki T, Ikeda N, Kamiryo T, Aoki H (1990) Nucleolar organizer regions in meningioma. Neurosurgery 26:43–46
Prysor-Jones RA, Jenkins JS (1981) Effect of bromocriptine on DNA synthesis, growth and hormone secretion of spontaneous pituitary tumours in rats. J Endocrinol 88:463–469
Rüschoff J, Plate K, Bittinger A, Thomas C (1989) Nucleolar organizer regions (NORs). Basic concepts and practical application in tumor pathology. Pathol Res Pract 185:878–885
Sasaki K, Ogino T, Takahashi M (1986) Immunological determination of labeling index on human tumor tissue sections using monoclonal anti-BrdUrd antibody. Stain Technol 61:155–161
Scheithauer BW, Randall RV, Laws ER Jr, Kovacs KT, Horvath E, Whitaker MD (1985) Prolactin cell carcinoma of the pituitary. Clinicopathologic, immunohistochemical, and ultrastructural study of a case with cranial and extracranial metastases. Cancer 55:598–604
Scheithauer BW, Kovacs KT, Laws ER Jr, Randall RV (1986) Pathology of invasive pituitary tumors with special reference to functional classification. J Neurosurg 65:733–744
Selman WR, Laws ER Jr, Scheithauer BW, Carpenter SM (1986) The occurrence of dural invasion in pituitary adenomas. J Neurosurg 64:402–407
Shibuya M, Hoshino T, Ito S, Wacker MR, Prados MD, Davis RL, Wilson CB (1992) Meningiomas: clinical implications of a high proliferative potential determined by bromodeoxyuridine labeling. Neurosurgery 30:494–498
Shibuya M, Miwa T, Hoshino T (1992) Embedding and fixation techniques for immunohistochemical staining with anti-DNA polymerase α and Ki-67 monoclonal antibodies to analyze the proliferative potential of tumors. Biotechnic Histochem (in press)
Stefaneanu L, Horvath E, Kovacs K (1989) Argyrophil organizer region proteins (AgNORs) in adenohypophysial cells and adenomas of the human pituitary. Mod Pathol 2:192–199
Vlahovitch B, Reynaud C, Rhiati J, Hammoud F (1988) Treatment and recurrence in 135 pituitary adenomas. Acta Neurochir (Wien) [Suppl] 42:120–123
Author information
Authors and Affiliations
Additional information
Supported by grants CA-13525 and CA-50210 from the National Cancer Institute, by a grant from the Phi Beta Psi Sorority, and by Grant-in-Aid A 63771083 from the Ministry of Education, Science, and Culture of Japan
Rights and permissions
About this article
Cite this article
Shibuya, M., Saito, F., Miwa, T. et al. Histochemical study of pituitary adenomas with Ki-67 and anti-DNA polymerase α monoclonal antibodies, bromodeoxyuridine labeling, and nucleolar organizer region counts. Acta Neuropathol 84, 178–183 (1992). https://doi.org/10.1007/BF00311392
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00311392