CHROMOSOME-17 ALLELIC LOSS IN ASTROCYTIC TUMORS AND ITS CLINICOPATHOLOGICAL IMPLICATIONS

To prognosticate the implications of various allelic losses on chromos ome 17 in the morphology and biology of astrocytic tumors, we have exa mined loss of heterozygosity (LOH) at 14 microsatellite loci on chromo some 17 in a series of 19 astrocytic tumors (3 astrocytomas, 5 anaplas tic astrocytomas, and 11 glioblastomas). The DNA samples extracted fro m tumor and matched normal brain tissue were amplified by polymerase c hain reaction (PCR) followed by polyacrylamide gel electrophoresis and photography under UV transillumination. The molecular genetic data we re compared with immunohistochemistry performed with antibodies to gli al fibrillary acidic protein (GFAP), MIB-1 and p53 protein. LOH was ob served in 11/19 (58%) instances with frequent involvement of TP53, NF1 , and D17S795 loci, LOH at D17S578 and D17S520 occurred in recurrent t umors exclusively. Allelic status of D17S795 in all 12 informative ins tances were concordant with GFAP immunoreactivity (p < 0.01, Fisher's test). p53 immunopositivity (> 25% of tumor cell nuclei) was seen in 1 1 (58%) tumors, of which 6 were informative of TP53 locus with 2 (33%) demonstrating LOH. The MIB-1 staining indexes in astrocytomas, anapla stic astrocytomas, and glioblastomas were 1.9 +/- 0.9, 8.4 +/- 4.0, an d 17.1 +/- 7.1% (mean +/- SD), respectively, and their differences wer e statistically significant (p < 0.05, Student's t test). A trend of i nverse relationship between patient survival and the number of tumor c ell nuclei with immunohistochemically detectable p53 protein was seen in glioblastoma cases: 20.5 +/- 12.7 versus 13.7 +/- 6.3 months (mean +/- SD) in instances with > or greater than or equal to 25% positive c ells, respectively. We conclude, the intriguing correlation between al lelic status of D17S795 microsatellite locus and GFAP immunoreactivity suggests the possible involvement of q21.2 segment of chromosome 17 i n the morphology and biology of astrocytic tumors.