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 im munohistochemically investigated for expression of transforming growth factor-alpha (TGF-alpha), epidermal growth factor receptor (EGF-R) an d oncoprotein c-erbR-2 by semiquantitative assessment. Proliferative a ctivity 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 cel ls increased with histologic malignancy. There was no expression of EG F-R and c-erbB-2 in the majority of low-grade astrocytomas. However, s mall focal expressions of TGF-alpha and EGF-R were observed in several low-grade astrocytomas (11/25), suggesting an early stimulation of ma lignant transformation. With regard to percentage, a strong positive c orrelation between TGF alpha and EGF-R-stained cells was found, indica ting an autocrine stimulation of the mitogenic pathway of the TGF-alph a/EGF-R system. Likewise, indices of EGF-R and c-erbB-2 positive cells correlated significantly. Less significant correlations were also sf en between EGF-R, c-erbB-2 frequencies and the Ki-67 labeling index. H owever, 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 thei r receptors or mutant EGF-R might participate in the proliferative act ivity of gliomas.