Evaluation of the expression of C-kit (CD117) in ependymomas and oligodendrogliomas.

C-kit is a proto-oncogene located on the long arm of chromosome 4. Its product, CD117, is a specific immunohistochemical (IHQ) marker that is associated with response to a potent tyrosine kinase inhibitor therapy with STI-571 (Gleevec®) in chronic myelogenous leukemia and GISTs. In our study, we aimed to evaluate the expression of CD117 in glial tumors as this finding may guide therapeutic approaches for these brain tumors. Ependymomas and oligodendrogliomas, in formalin fixed and paraffin embedded blocks were assayed for CD117 immunoreactivity using anti-c-kit (CD117, DAKO). GISTs were used as positive control. We observed immunoreactivity of CD117 protein in 25.5% of tumors in both histological types. In oligodendrogliomas, there was an association between older age at diagnosis and positivity for CD117 (P=0.039). In addition, we observed an association between higher tumor grade (grade III) and positivity for CD117 (P=0.007). No clinical association was observed in ependymomas (P>0.05). This study encourages further investigations, considering that CD117 may be a possible oncogenic factor in some glial tumors. In this case, tumors that express this marker may eventually benefit from a therapy with selective inhibitors of receptor kinases.

Immunohistochemical evaluation of the microvascular density through the expression of TGF-beta (CD 105/endoglin) and CD 34 receptors and expression of the vascular endothelial growth factor (VEGF) in oligodendrogliomas.

Angiogenesis has been proposed as essential for the growth of solid tumors. The determinants of this process, the growth factors and the vascular endothelial receptors have brought a potential in the tumor prognostic determination as well as perspectives of "targets" for antiangiogenic therapy. In oligodendrogliomas (OL), angiogenesis is little known and/or has generated conflicting results. In order to clarify angiogenesis in OL, we have evaluated the immunohistochemical expression of vascular endothelial growth factor (VEGF) and the microvascular density (MVD) through the expression of TGF-beta (CD105/endoglin) (MVD-CD105) and CD34 (MVD-CD34) receptors using the Chalkley point method in 30 OL. No significant immune reaction was found for the VEGF. There was expression in <10% of tumor cells and/or staining of weak intensity in 15 (50.0%), >10% of cells and moderate intensity staining in 1 (3.33%), and negative expression in 14 (46.67%). If present, the expression was restricted to tumor and endothelial cells. Our findings suggest that VEGF has little influence on OL angiogenesis. All specimens showed CD105 and CD34 expression in the intratumor vascular endothelium, suggesting involvement of CD105 in OL angiogenesis. The mean +/- SD MVD-CD105 and MVD-CD34 were 10.83 +/- 2.24 and 11.00 +/- 2.76 in OL (P = 0.086; r = 0.319); 10.00 +/- 2.00 and 10.40 +/- 3.02 in OL grade II (n = 15) (P = 0.547; r = 0.105), and 11.67 +/- 2.22 and 11.53 +/- 2.45 in OL grade III (n = 15) (P = 0.817; r = 0.551), respectively. The absence of correlation between DMV-CD105, DMV-CD34 and tumor grades suggests that anti-CD105 and anti-CD34 antibodies have different vascular specificities. MVD-CD105 was greater in OL grade III than in OL grade II (P = 0.0032), indicating an increase in the vascular neoformation, something which must be evaluated as a possible prognostic factor in OL. Both TGF-beta and CD105 bring perspectives as "targets" for antiangiogenic treatments in OL.

[Immunohistochemistry in oligodendrogliomas]. / Imunoistoquímica em oligodendrogliomas.

Oligodendrogliomas (OL) are neuroepithelial tumors characterized by the presence of uniformly round nuclei with a clear cytoplasm around it. These features can also be seen in central neurocytomas, DNTs and clear cell ependymomas. Immunohistochemistry with glial and neuronal markers may be helpful in differential diagnosis. The aim of this study was to determine the glial and neuronal differentiation in 42 specimens of otherwise typical OL using immunohistochemical techniques. Ten cases showed anaplastic characteristics. Thirty-three samples (78.5%) were positive to GFAP with few cells stained in ten cases and many positive cells in six. Twelve cases (28.5%) were focally positive to NSE and/or synaptophysin showing neuronal differentiation. Thirty-four cases (80.9%) expressed S-100. In conclusion, glial proteins may be present focally in OL due to presence of mature reactive astrocytes or transitional forms between astrocytes and oligodendrocytes. Focal areas of neuronal differentiation can also be found in typical OL. The widespread staining with neuronal marker suggests central neurocytoma, but this diagnosis should not be done with small amount of tissue.