Summary
The expression of transferrin receptor (Tr) was investigated by means of immunohistochemistry in 101 tumours of the human central and peripheral nervous system. The results were compared with the proliferative activity of the tumours, determined by immunostaining for the proliferation-associated antigen Ki-67. In addition to immunostaining of normal and proliferated blood vessel endothelium and of a fraction of tumour infiltrating lymphocytes, we observed staining for Tr in a variable fraction of neoplastic cells of all histological tumour types. Immunoreactivity in the majority of tumour cells was found only in anaplastic tumours such as glioblastomas. Furthermore, a positive correlation between Tr expression and the Ki-67 growth fraction was established for gliomas. Non-glial tumours strongly expressing Tr included one metastatic rhabdomyosarcoma, one intracerebral malignant lymphoma, two of four plasmocytomas and seven of nine metastatic carcinomas. Our results indicate that immunohistochemistry for Tr and Ki-67 can provide additional information about the biological behaviour of nervous system tumours, thus complementing conventional histopathological criteria for anaplasia.
Similar content being viewed by others
References
Barnett D, Wilson GA, Lawrence AC, Buckley GA (1987) Transferrin receptor expression in the leukaemias and lymphoproliferative disorders. Clin Lab Haematol 9:361–370
Colombatti M, Bisconti M, Dell'Arciprete L, Gerosa MA, Tridente G (1988) Sensitivity of human glioma cells to cytotoxic heteroconjugates. Int J Cancer 42:441–448
Dautry-Varsat A, Ciechanover A, Lodish HG (1983) pH and the recycling of transferrin during receptor mediated endocytosis. Proc Natl Acad Sci USA 80:2258–2262
Deckert M, Reifenberger G, Wechsler W (1989) Determination of the proliferative potential of human brain tumors using the monoclonal antibody Ki-67. J Cancer Res Clin Oncol 115:179–188
Doria MI Jr, Montag AG, Franklin WA (1988) Immunophenotype of small cell lung carcinoma. Expression of NKH-1 and transferrin receptor and absence of most myeloid antigens. Cancer 62:1939–1945
Gatter KC, Brown G, Trowbridge IS, Woolston R-E, Mason DY (1983) Transferrin receptors in human tissues: their distribution and possible clinical relevance. J Clin Pathol 36:539–535
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 HH, 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
Hamilton TA (1982) Regulation of transferrin receptor expression in concanavalian A stimulated and Gross virus transformed rat lymphoblasts. J Cell Physiol 113:40–46
Hsu SM, Raine L, Fanger H (1981) The use of anti-avidin antibody and avidin-biotin-peroxidase-complex in immunoperoxidase techniques. Am J Clin Pathol 75:816–821
Jefferies WA, Brandon MR, Hunt SV, Williams AF, Gatter KC, Mason DY (1984) Transferrin receptor on endothelial cells of brain capillaries. Nature 312:162–163
Johnson VG, Wrobel C, Wilson D, Zovickian J, Greenfield L, Oldfield EH, Youle R (1989) Improved tumor-specific immunotoxins in the treatment of CNS and leptomeningeal neoplasia. J Neurosurg 70:240–248
Klausner RD, Ashwell G, Renswoude J van, Harford JB, Bridges KR (1983a) Binding of apotransferrin to K562 cells: explanation of the transferrin cycle. Proc Natl Acad Sci USA 80:2263–2266
Klausner RD, Renswoude J van, Ashwell G, Kempf C, Schechter AN, Dean A, Bridges KR (1983b) Receptor mediated endocytosis of transferrin in K562 cells. J Biol Chem 258:4715–4724
Kleihues P, Meer L, Shibata T, Bamberg M (1988) DNA-Reparatur und DNA-Replikation als Kriterien für therapeutische Effizienz. In: Bamberg S, Sack H (eds) Therapie primärer Hirntumoren, Zuckschwerdt, Munich, pp 1–8
Kvaloy S, Langholm R, Kaalhus O, Michaelsen T, Funderud S, Foss Abrahamsen A, Godal T (1984) Transferrin receptor and B-lymphoblast antigen: their relationship to DNA synthesis, histology and survival in B-cell lymphomas. Int J Cancer 33:173–177
Larrick JW, Creswell P (1979) Modulation of cell surface iron transferrin receptors by cellular density and state of activation. J Supramol Struct 11:579–586
Neckers LM, Yenokida G, James SP (1984) The role of transferrin receptor in human B lymphocyte activation. J Immunol 133:2437–2441
Niitsu Y, Kohgo Y, Nishisato T, Kondo H, Kato J, Urushizaki Y, Urushizaki I (1987) Transferrin receptors in human cancerous tissues. Tohoku J Exp Med 153:239–243
Medeiros LJ, Picker LJ, Horning SJ, Warnke RA (1988) Transferrin receptor expression by non-Hodgkin's lymphomas. Correlation with morphologic grade and survival. Cancer 61:1844–1851
Prior R, Reifenberger G, Wechsler W (1989) Nerve growth factor receptor in tumours of the human nervous system. Immunohistochemical analysis of receptor expression and tumour growth fraction. Pathol Res Pract 185:332–338
Reifenberger G, Prior R, Deckert M, Wechsler W (1989) Epidermal growth factor receptor expression and growth fraction in human tumours of the nervous system. Virchows Arch [A] 414:147–155
Schneider C, Sutherland R, Newman R, Greaves M (1982) Structural features of the cell surface receptor for transferrin that is recognised by the monoclonal antibody OKT9. J Biol Chem 257:8516–8522
Schneider C, Owen M, Banville D, Williams JG (1984) Primary structure of human transferrin receptor deduced from the mRNA sequence Nature 311:675–678
Schrape S, Jones DB, Wright DH (1987) A comparison of three methods for the determination of the growth fraction in non-Hodgkin's lymphoma. Br J Cancer 55:283–286
Sciot R, Paterson AC, Eyken P van, Callea F, Kew MC, Desmet VJ (1988) Transferrin receptor expression in human hepatocellular carcinoma: an immunohistochemical study of 34 cases. Histopathology 12:53–63
Seymour GJ, Walsh MD, Lavin MF, Strutton G, Gardiner RA (1987) Transferrin receptor expression by human bladder transitional cell carcinomas. Urol Res 15:341–344
Soyer HP, Smolle J, Torne R, Kerl H (1987) Transferrin receptor expression in normal skin and in various cutaneous tumors. J Cutan Pathol 14:1–5
Trowbridge IS, Newman RA, Domingo DL, Sauvage C (1984) Transferrin receptors: structure and function. Biochem Pharmacol 33:925–932
Wain SL, Braylan RC, Borowitz MJ (1987) Correlation of monoclonal antibody phenotyping and cellular DNA content in non-Hodgkin's lymphoma. The Southeastern Cancer Study Group experience. Cancer 60:2403–24
Walker RA, Camplejohn RS (1986) DNA flow cytometry of human breast carcinomas and its relationship to transferrin and epidermal growth factor receptors. J Pathol 150:37–42
Winkler J, Roosen N, Reifenberger G, Wechsler W (1988) Dedifferentiation in recurrent astrocytoma: clinicopathological study of two cases (abstract). Clin Neuropathol 7:222
Wrba F, Ritzinger E, Reiner A, Holzner JH (1986) Transferrin receptor (TrfR) expression in breast carcinoma and its possible relationship to prognosis. An immunohistochemical study. Virchows Arch [A] 410:69–73
Wrba F, Reiner A, Markis-Ritzinger E, Holzner JH, Reiner G, Spona J (1988) Prognostic significance of immunohistochemical parameters in breast carcinomas. Pathol Res Pract 183:277–283
Zovickian J, Johnson VG, Youle RJ (1987) Potent and specific killing of human malignant brain tumor cells by an antitransferrin receptor antibody-ricin immunotoxin. J Neurosurg 66:850–861
Zülch KJ (1979) Histological typing of tumours of the central nervous system. International histological classification of tumours. WHO, Geneva
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Prior, R., Reifenberger, G. & Wechsler, W. Transferrin receptor expression in tumours of the human nervous system: relation to tumour type, grading and tumour growth fraction. Vichows Archiv A Pathol Anat 416, 491–496 (1990). https://doi.org/10.1007/BF01600299
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01600299