Summary
Epidermal growth factor and its receptor (EGFR) constitute an important and well-characterized mitogenic system in various ectodermal tissues including glial cells. Over-expression of the EGFR due to gene amplification has been reported in primary brain tumours of glial origin. Using a monoclonal antibody to the EGFR and immunohistochemical analysis, we examined the expression and distribution of EGFR in 103 astrocytic tumours. In addition, selected tumours were studied by Western blotting using a polyclonal antibody to EGFR and by Southern blot analysis. Glioblastomas (WHO grade IV) showed EGFR expression in 37% of cases, whereas pilocytic (WHO grade I), low-grade (WHO grade II) or anaplastic astrocytoma (WHO grade III) were invariably EGFR negative. Generally, there was a close correlation between the presence of EGFR gene amplification and over-expression of receptor protein. Different patterns of immunoreactive cells and significant intratumour heterogeneity of EGFR expression were observed in glioblastomas. The specific association of EGFR over-expression with glioblastoma may provide a useful diagnostic tool for distinguishing anaplastic astrocytoma (WHO grade III) and glioblastoma multiforme (WHO grade IV).
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References
Arita N, Hayakawa T, Izumoto S, Taki T, Ohnishi T, Yamamoto H, Bitoh S, Mogami H (1989) Epidermal growth factor receptor in human glioma. J Neurosurg 70:916–919
Ausubel FM, Brent R, Kinston RE, Moore DD, Seidman JD (1987) Current protocols in molecular biology. Wiley, New York-Toronto-Singapore, pp 2.2.1–2.2.2
Bigner SH, Vogelstein B (1990) Cytogenetics and molecular genetics of malignant gliomas and medulloblastoma. Brain Pathol 1:12–18
Bigner SH, Wong AJ, Mark J, Muhlbaier LH, Kinzler KW, Vogel-stein B, Bigner DD (1987) Relationship between gene amplification and chromosomal deviations in malignant human gliomas. Cancer Genet Cytogenet 29:165–170
Bruce JN, Duigou GJ, Fisher PB (1988) Expression of the epidermal growth factor receptor (EGFR) in primary brain tumors. Cold Spring Harbor Meeting on Cancer Cells, vol 1. Cold Spring Harbor Laboratory, Cold Spring Harbor, p 54
Deimling A von, Louis DN, Ammon K von, Petersen I, Hoell T, Chung RY, Martuza RL, Schoenfeld DA, Yasargil GM, Wiestler OD, Scizinger BR (in press) Epidermal growth factor receptor gene amplification in human glioblastoma multiforme is invariably associated with loss of chromosome 10. J Neurosurg
Downward J, Yarden Y, Scrace G, Totty N, Stockwell N, Ullrich A, Schlessinger J, Waterfield MD (1984) Close similarity of epidermal growth factor receptor and v-erb B oncogene protein sequences. Nature 307:512–527
Ekstrand AJ, James CDE, Cavenee WK, Seliger B, Pettersson RF, Collins VP (1991) Genes for epidermal growth factor receptor, transforming growth factor alpha, and epidermal growth factor and their expression in human gliomas in vivo. Cancer Res 51:2164–2172
Feinberg AP, Vogelstein B (1983) DNA extraction and labelling. Anal Biochem 132:6–13
Gerosa MA, Talarico D, Fognani C, Raimondi E, Colombatti M, Tridente G, De Carli L, Della Valle G (1989) Overexpression of N-ras oncogene and epidermal growth factor receptor gene in human glioblastomas. J Natl Cancer Inst 81:63–67
Gullick WJ, Marsden JJ, Whittle N, Ward B, Bobrow L, Waterfield MD (1986) Expression of epidermal growth factor receptors on human cervical, ovarian, and vulval carcinomas. Cancer Res 46:285–292
Hall WA, Merrill MJ, Walbridge S, Youle RJ (1990) Epidermal growth factor receptors on ependymomas and other brain tumors. J Neurosurg 72:641–646
Hawkins RA, Killen ER, Jack WJ, Chetty U (1991) Epidermal growth factor receptors in intracranial and breast tumours: their clinical significance. Br J Cancer 63:553–560
Hunter T, Cooper JA (1985) Protein tryrosine kinases. Annu Rev Biochem 54:879–930
Kleihues P, Burger PC, Scheithauer BW (1992) Histologic typing of tumors of the central nervous system, 2nd edn. Springer, Berlin Heidelberg New York
Kris RM, Lax I, Gullick WJ, Waterfield MD, Ullrich A, Fridkin M, Schlessinger J (1985) Antibodies against a synthetic peptides as a probe for the kinase activity of the avian EGF receptor and v-erb B protein. Cell 40:619–625
Libermann TA, Razon N, Bartal AD, Yarden Y, Schlessinger J, Soreq H (1984) Expression of epidermal growth factor receptors in human brain tumors. Cancer Res 46:285–292
Libermann TA, Nusbaum H, Razon N, Kris R, Lax I, Soreq H, Whittle N, Waterfield MD, Ullrich A, Schlessinger J (1985) Amplification, enhanced expression, and possible rearrangement of the EGF-receptor gene in primary human brain tumours of glial origin. Nature 313:144–147
Malden LT, Novak U, Kaye AH, Burgess AW (1988) Selective amplification of the cytoplasmic domain of the epidermal growth factor receptor gene in glioblastoma multiforme. Cancer Res 48:2711–2714
Maniatis T, Fritsch EF, Sambrook J (1989) Molecular cloning, 2nd edn. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 9.31–9.62
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
Reubi JC, Horisberger U, Lang W, Koper JW, Braakman R, Lamberts SWJ (1989) Coincidence of EGF receptors and somatostatin receptors in meningiomas but inverse, differentiation-dependent relationship in glial tumors. Am J Pathol 134:337–344
Ro J, North SM, Gullick GE, Hortobagyi GN, Gutterman JU, Blick M (1988) Amplified and overexpressed epidermal growth factor receptor gene in uncultured primary human breast carcinoma. Cancer Res 48:161–164
Sternberger LA (1982) Immunohistochemistry, 3rd edn. Wiley, New York-Toronto-Singapore
Strommer K, Hamou MF, Diggelmann H, Tribolet N de (1990) Cellular and tumoural heterogeneity of EGFR gene amplification in human malignant gliomas. Acta Neurochir (Wien) 107:82–87
Torp SH, Helseth E, Dalen A, Unsgaard G (1991) Epidermal growth factor receptor expression in human gliomas. Cancer Immunol Immunother 33:61–64
Zülch KJ (1979) Histological typing of tumors of the central nervous system. International classification of tumours. Springer, Berlin Heidelberg New York
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Agosti, R.M., Leuthold, M., Gullick, W.J. et al. Expression of the epidermal growth factor receptor in astrocytic tumours is specifically associated with glioblastoma multiforme. Vichows Archiv A Pathol Anat 420, 321–325 (1992). https://doi.org/10.1007/BF01600211
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DOI: https://doi.org/10.1007/BF01600211