Acta
Acta Neuropathol (1990) 79 : 418 - 423
Neuropathologca 9 Springer-Verlag 1990
Localization of basic fibroblast growth factor, a mitogen and angiogenic factor, in human brain tumors W. Paulus 1, C. Grothe 2, M. Sensenbrenner a, T. Janet a, I. Baur 1, M. Graf l, and W. Roggendorf 1 1 Institut ffir Hirnforschung, Universit/it Tiibingen, Federal Republic of Germany 2 Institut ftir Anatomic und Zellbiologie, Universit/it Marburg, Federal Republic of Germany 3 Centre de Neurochimie du C.N.R.S., Strasbourg, France
Summary. Fibroblast growth factor (FGF) is a potent angiogenic factor and a mitogen for a variety of mesoderm- and neuroectoderm-derived cell types (e. g., fibroblasts, endothelial cells, astrocytes, oligodendrocytes). After application of a monospecific polyclonal antiserum, we localized basic FGF on frozen sections o f 73 human brain tumors using immunohistochemistry. FGF was present in a variable number of tumor cells (16/16 astrocytomas, 5/5 ependymomas, 0/3 benign and 4/7 anaplastic oligodendrogliomas, 11/12 glioblastomas, 11/11 meningiomas, 6/6 neurilemmomas, 0/3 pituitary adenomas, 2/2 choroid plexus papillomas, 0/1 neurocytoma, 2/2 benign fibrous histiocytomas, 2/5 metastatic carcinomas). FGF was detected in vascular cells of 59 tumors and in fibroblasts of connective tissue stroma from all papillomas and metastases. These results tend to indicate FGF involvement in the malignant progression of gliomas due to an autocrine or paracrine action. Histopathological aspects of malignant gliomas (e. g., pseudopalisading or pathological vessels) could be related to FGF activity. Key words: Fibroblast growth factor (FGF) - Basic FGF - Angiogenesis - Brain tumors - Immunohistochemistry
Fibroblast growth factor (FGF), which exists in two closely related proteinaceous forms (basic and acidic), was first isolated from normal bovine brain and pituitary. It is a mitogen for a variety of mesodermand neuroectoderm-derived cell types including fibroblasts, endothelial cells, astrocytes, and oligoOffprint requests to: W. Paulus 7 Ludwig Boltzmann Institut ffir Klinisehe Neurobiologie, Krankenhaus Lainz, Wolkersbergenstrasse 1, A-1130 Wien, Austria
dendrocytes (for review, see [11, 12, 39, 50]). In rat glial cell cultures, FGF induces proliferation [37, 38, 53], development of intermediate filament bundles and cell processes [54], decrease of orthogonal arrays of particles [56], release of plasminogen activators [42], and increase of different proteins such as glial fibrillary acidic protein (GFAP) [30, 36], S-100 protein [54], glutamine synthetase [37, 38] and carbonic anhydrase [51. Evidence is available for FGF involvement in the malignant progression of human gliomas. A proliferative effect on cultured glioma cells [55] and the expression of the acidic FGF (aFGF) gene and FGF receptors in glioma cell lines have been reported [24]. Since FGF is one of the most potent angiogenic factors [9], it could be responsible for the massive proliferation of vascular cells in malignant gliomas. While FGF has been demonstrated in neuronal [21], adenohypophyseal [2], astroglial [7, 15], endothelial [45, 46], vascular smooth muscle [13], astrocytoma [45], neuroblastoma [18], medulloblastoma [25], and extracerebral tumor cell lines [26, 31, 47, 51] as well as in vivo in neurons of the normal rat and bovine brain [18, 20, 40] and in reactive astrocytes [8], no information is available on the cellular distribution of FGF in brain tumors. Therefore, we investigated the immunohistochemical expression and localization of basic FGF (bFGF) in a series of human intracranial tumors of glial and nonglial origin.
Materials and methods Human intracranial tumors (n = 73) of patients undergoing surgery between May 1986 and March 1989 were examined (see Table 1). Tissue was frozen in isopentane/liquid nitrogen within 10 min of removal and stored at - 7 2 ~ Diagnoses were made on paraffin sections. Polyclonal rabbit anti-bFGF antiserum was raised against purified bovine pituitary bFGF. b F G F was kindly provided by Dr. D. Gospodarowicz, San Francisco. The antibody was characterized in enzyme-linked immunosorbent
w. Paulus et al. : Basic fibroblast growth factor in brain tumors
419
Table 1. Fibroblast growth factor (FGF) expression in 73 brain tumors Number of tumors: grade (WHO)
Pilocytic astrocytoma Astrocytoma Anaplastic astrocytoma Oligodendroglioma Anapl. oligodendrolioma Ependymoma Anaplastic ependymoma Glioblastoma Meningioma Malignant meningioma Neurilemmoma Pituitary adenoma Plexus papilloma Neurocytoma Benign fibr. histiocytoma Metastatic carcinoma Total
I II III II III II III IV I III I I I -
Total
with tumor cells positive for FGF; percentage of positive tumor cells:
Acta Neuropathol (1990) 79 : 418 - 423
Neuropathologca 9 Springer-Verlag 1990
Localization of basic fibroblast growth factor, a mitogen and angiogenic factor, in human brain tumors W. Paulus 1, C. Grothe 2, M. Sensenbrenner a, T. Janet a, I. Baur 1, M. Graf l, and W. Roggendorf 1 1 Institut ffir Hirnforschung, Universit/it Tiibingen, Federal Republic of Germany 2 Institut ftir Anatomic und Zellbiologie, Universit/it Marburg, Federal Republic of Germany 3 Centre de Neurochimie du C.N.R.S., Strasbourg, France
Summary. Fibroblast growth factor (FGF) is a potent angiogenic factor and a mitogen for a variety of mesoderm- and neuroectoderm-derived cell types (e. g., fibroblasts, endothelial cells, astrocytes, oligodendrocytes). After application of a monospecific polyclonal antiserum, we localized basic FGF on frozen sections o f 73 human brain tumors using immunohistochemistry. FGF was present in a variable number of tumor cells (16/16 astrocytomas, 5/5 ependymomas, 0/3 benign and 4/7 anaplastic oligodendrogliomas, 11/12 glioblastomas, 11/11 meningiomas, 6/6 neurilemmomas, 0/3 pituitary adenomas, 2/2 choroid plexus papillomas, 0/1 neurocytoma, 2/2 benign fibrous histiocytomas, 2/5 metastatic carcinomas). FGF was detected in vascular cells of 59 tumors and in fibroblasts of connective tissue stroma from all papillomas and metastases. These results tend to indicate FGF involvement in the malignant progression of gliomas due to an autocrine or paracrine action. Histopathological aspects of malignant gliomas (e. g., pseudopalisading or pathological vessels) could be related to FGF activity. Key words: Fibroblast growth factor (FGF) - Basic FGF - Angiogenesis - Brain tumors - Immunohistochemistry
Fibroblast growth factor (FGF), which exists in two closely related proteinaceous forms (basic and acidic), was first isolated from normal bovine brain and pituitary. It is a mitogen for a variety of mesodermand neuroectoderm-derived cell types including fibroblasts, endothelial cells, astrocytes, and oligoOffprint requests to: W. Paulus 7 Ludwig Boltzmann Institut ffir Klinisehe Neurobiologie, Krankenhaus Lainz, Wolkersbergenstrasse 1, A-1130 Wien, Austria
dendrocytes (for review, see [11, 12, 39, 50]). In rat glial cell cultures, FGF induces proliferation [37, 38, 53], development of intermediate filament bundles and cell processes [54], decrease of orthogonal arrays of particles [56], release of plasminogen activators [42], and increase of different proteins such as glial fibrillary acidic protein (GFAP) [30, 36], S-100 protein [54], glutamine synthetase [37, 38] and carbonic anhydrase [51. Evidence is available for FGF involvement in the malignant progression of human gliomas. A proliferative effect on cultured glioma cells [55] and the expression of the acidic FGF (aFGF) gene and FGF receptors in glioma cell lines have been reported [24]. Since FGF is one of the most potent angiogenic factors [9], it could be responsible for the massive proliferation of vascular cells in malignant gliomas. While FGF has been demonstrated in neuronal [21], adenohypophyseal [2], astroglial [7, 15], endothelial [45, 46], vascular smooth muscle [13], astrocytoma [45], neuroblastoma [18], medulloblastoma [25], and extracerebral tumor cell lines [26, 31, 47, 51] as well as in vivo in neurons of the normal rat and bovine brain [18, 20, 40] and in reactive astrocytes [8], no information is available on the cellular distribution of FGF in brain tumors. Therefore, we investigated the immunohistochemical expression and localization of basic FGF (bFGF) in a series of human intracranial tumors of glial and nonglial origin.
Materials and methods Human intracranial tumors (n = 73) of patients undergoing surgery between May 1986 and March 1989 were examined (see Table 1). Tissue was frozen in isopentane/liquid nitrogen within 10 min of removal and stored at - 7 2 ~ Diagnoses were made on paraffin sections. Polyclonal rabbit anti-bFGF antiserum was raised against purified bovine pituitary bFGF. b F G F was kindly provided by Dr. D. Gospodarowicz, San Francisco. The antibody was characterized in enzyme-linked immunosorbent
w. Paulus et al. : Basic fibroblast growth factor in brain tumors
419
Table 1. Fibroblast growth factor (FGF) expression in 73 brain tumors Number of tumors: grade (WHO)
Pilocytic astrocytoma Astrocytoma Anaplastic astrocytoma Oligodendroglioma Anapl. oligodendrolioma Ependymoma Anaplastic ependymoma Glioblastoma Meningioma Malignant meningioma Neurilemmoma Pituitary adenoma Plexus papilloma Neurocytoma Benign fibr. histiocytoma Metastatic carcinoma Total
I II III II III II III IV I III I I I -
Total
with tumor cells positive for FGF; percentage of positive tumor cells:
