NECROGENESIS AND FAS APO-1 (CD95) EXPRESSION IN PRIMARY (DE-NOVO) ANDSECONDARY GLIOBLASTOMAS/

Glioblastomas may develop rapidly without clinical and histopathologic al evidence of a less malignant precursor lesion (de novo or primary g lioblastoma) or through progression from low-grade or anaplastic astro cytoma (secondary glioblastoma). Primary glioblastomas typically show overexpression of EGFR, but rarely p53 mutations, while secondary glio blastomas frequently carry a p53 mutation, but usually lack overexpres sion of EGFR, suggesting that these glioblastoma subtypes develop thro ugh distinct genetic pathways. In the present study, we assessed the e xpression of Fas/APO-1 (CD95), an apoptosis-mediating cell membrane pr otein, and its relation to necrosis phenotype in primary and secondary glioblastomas. Large areas of ischemic necroses were observed in all 18 primary glioblastomas, but were significantly less frequent in seco ndary glioblastomas (10 of 19, 53%; p = 0.0004). Fas expression was pr edominantly observed in glioma cells surrounding large areas of necros is and was thus significantly more frequent in primary glioblastomas ( 18 of 18, 100%) than in secondary glioblastomas (4 of 19, 21%; p < 0.0 001), suggesting that these clinically and genetically defined subtype s of glioblastoma differ in the extent and mechanism of necrogenesis. Necrosis and microvascular proliferation are histologic hallmarks of t he glioblastoma. Following incubation of glioblastoma cell lines under hypoxic/anoxic conditions for 24-48 hours, Fas mRNA levels remained u nchanged, whereas VEGF expression was markedly upregulated. This sugge sts that in contrast to VEGF, Fas expression is not induced by ischemi a/hypoxia. Analysis of Fas mRNA levels in a glioblastoma cell line con taining a p53 mutation and an inducible wild-type p53 gene showed litt le difference under induced and noninduced conditions, suggesting that in glioblastomas, Fas expression is not directly linked to the p53 st atus.