Correlation of TGF-alpha and EGF-receptor expression with proliferative activity in human astrocytic gliomas.
Fifty-nine paraffin-embedded astrocytic gliomas (four WHO grade 1, 21 WHO grade 2, 17 WHO grade 3 and 17 glioblastomas, WHO grade 4) were immunohistochemically investigated for expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R) and oncoprotein c-erbB-2 by semiquantitative assessment. Proliferative activity was simultaneously analyzed by using the antibody Ki-67 (MIB-1). Immunostaining in neoplastic cells was quantified by image analysis. Concerning the antibodies used, the percentage of immunoreactive cells increased with histologic malignancy. There was no expression of EGF-R and c-erbB-2 in the majority of low-grade astrocytomas. However, small focal expressions of TGF-alpha and EGF-R were observed in several low-grade astrocytomas (11/25), suggesting an early stimulation of malignant transformation. With regard to percentage, a strong positive correlation between TGF-alpha and EGF-R-stained cells was found, indicating an autocrine stimulation of the mitogenic pathway of the TGF-alpha/EGF-R system. Likewise, indices of EGF-R and c-erbB-2 positive cells correlated significantly. Less significant correlations were also seen between EGF-R, c-erbB-2 frequencies and the Ki-67 labeling index. However, there was no correlation between TGF-alpha and Ki-67 indices. The results suggest that TGF-alpha expression is not directly related to the proliferative potential as judged by the Ki-67 labeling index. Furthermore, besides EGF-R and c-erbB-2, other growth factors and their receptors or mutant EGF-R might participate in the proliferative activity of gliomas.
von Bossanyi
P
P
Department of Neuropathology, University of Magdeburg, Germany.
Sallaba
J
J
Dietzmann
K
K
Warich-Kirches
M
M
Kirches
E
E
D001254:Astrocytoma / Q000378:metabolism* / Q000473:pathology; D001932:Brain Neoplasms / Q000378:metabolism* / Q000473:pathology; D002452:Cell Count; D002455:Cell Division; D066246:ErbB Receptors / Q000378:metabolism*; D005909:Glioblastoma / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D019394:Ki-67 Antigen / Q000378:metabolism; D008940:Mitotic Index; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism*
D066246:ErbB Receptors; D019394:Ki-67 Antigen; D018719:Erb-b2 Receptor Tyrosine Kinases; D016211:Transforming Growth Factor alpha