TP53 gene mutations, nuclear p53 accumulation, expression of waf/p21, bcl-2, and CD95 (APO-1/Fas) proteins are not prognostic factors in de novo glioblastoma multiforme

Glioblastoma multiforme (WHO grade IV; GBM) is the most common primary brai n tumor with a median survival of less than one year despite multimodal tre atment regimens. However, a small subgroup of GBM patients has a better cli nical outcome, with a small number of patients surviving several years. Apo ptosis, a genetically determined program of cell suicide, may be induced as a consequence of critical DNA damage. However, due to defects in the signa ling pathways, cancer cells may escape apoptosis, despite carrying irrevers ible DNA damage. In the present study, we have analyzed tumors of two age-m atched, equally treated groups of GBM patients with different postoperative time to tumor progression (TTP), defined as 'short-term' for TTP of less t han 6 months (n = 54), and 'long-term' for TTP of more than 12 months (n = 39) for alterations in apoptosis regulatory pathways: Mutations of the TP53 tumor suppressor gene and/or nuclear accumulation of its gene product p53, expression of Waf/p21, CD95 (Apo1/Fas), and Bcl-2. TP53 mutations were fou nd in 12 out of 54 (22%) GBMs of short-term survivors and 8 out of 35 (23%) tumors of long-term survivors; the respective numbers for nuclear p53 prot ein accumulation were 12/53 (23%) and 10/37 (27%). Waf1/p21 expression was found in 13/53 (25%) tumors of short-term survivors and 9/35 (26%) GBMs of long-term survivors. The respective numbers for Bcl-2 expression were 25/42 (60%) and 22/36 (61%) and for CD95 (Apo1/Fas) expression 20/49 (41%) and 1 4/36 (39%) GBMs. The percentage of alterations in genes/proteins involved i n the apoptotic pathway investigated here was virtually identical in the tw o groups of clinically different GBM patients. Thus, our data imply that no ne of these alterations investigated per se has a strong impact on the over all survival of GBM patients.