Loss of Heterozigosity on 10q23 (PTEN Region) Is a Relevant Predictor of Survival in High Grade Astrocytomas
MA Idoate, J Echeveste, R Diez Valle, MD Lozano, B Bejarano. University of Navarra, Pamplona, Navarra, Spain
Background: PTEN is a suppressor gene located in the chromosome region 10q23.3 which is considered a genetic marker of glioblastomas. Loss of heterozigosity (LOH) around PTEN could be a relevant prognostic marker in high-grade astrocytomas, but a systematic study with a number of microsatellites is not available. We have realized a study of LOH of 10q23 in a large series of patients diagnosed of high-grade astrocytoma with a complete follow-up.
Design: Fifty-nine patients were operated and diagnosed as glioblastomas (43) and anaplastic astrocytomas (16) between 1994 and 2003. The mean age of these patients was 47 y.o. (6-78) and the mean of Karnofsky was 81%. All patients received the same protocol treatment. Twelve cases of diffuse grade II were also included as a reference, A LOH PCR analysis by using 4 microsatellites of 10q23.3 chromosome (D10S579, -S2491, -S541AF, -Ma086wg9) on frozen tumors was applied. LOH evaluation was made by two observers and the non-clear cases were studied by a semi-quantitative method according to international standard references. A statistical study was applied.
Results: Tumors with LOH deletion showed no distinctive histological features respect to those without deletions. A frequent LOH on 10q23,3 PTEN region was observed in 25%, 35% and 40% of grade III and in 23%, 46% and 31% of grade IV, tumors, according to 1, 2 or ≥3 deleted loci respectively. In grade II astrocytomas, no deletion was observed. In glioblastomas, the mean of overall survival after diagnosis was significant according to the number of deleted loci (905 days for no deleted loci against 205 days for patients with ≥3 deleted loci). A striking correlation between LOH deletion (≥ 1 locus deleted) around PTEN and overall survival was observed in both grade IV (Log-Rank, Mantel-Cox, p= 0.01) and grade III (Log-Rank, Mantel-Cox, p= 0.03) astrocytomas.
Conclusions: According to our results, LOH deletion on 10q23 is a strong marker of survival in high-grade astrocytomas, and it is not associated to distinctive tumor histological features.
Tuesday, March 23, 2010 1:00 PM
Platform Session: Section G, Tuesday Afternoon