Chromosome 17 allelic loss in astrocytic tumors and its clinico-pathologic implications.
To prognosticate the implications of various allelic losses on chromosome 17 in the morphology and biology of astrocytic tumors, we have examined loss of heterozygosity (LOH) at 14 microsatellite loci on chromosome 17 in a series of 19 astrocytic tumors (3 astrocytomas, 5 anaplastic astrocytomas, and 11 glioblastomas). The DNA samples extracted from tumor and matched normal brain tissue were amplified by polymerase chain reaction (PCR) followed by polyacrylamide gel electrophoresis and photography under UV transillumination. The molecular genetic data were compared with immunohistochemistry performed with antibodies to glial fibrillary acidic protein (GFAP), MIB-1 and p53 protein. LOH was observed in 11/19 (58%) instances with frequent involvement of TP53, NF1, and D17S795 loci, LOH at D17S578 and D17S520 occurred in recurrent tumors exclusively. Allelic status of D17S795 in all 12 informative instances were concordant with GFAP immunoreactivity (p < 0.01, Fisher's test). p53 immunopositivity (> 25% of tumor cell nuclei) was seen in 11 (58%) tumors, of which 6 were informative of TP53 locus with 2 (33%) demonstrating LOH. The MIB-1 staining indexes in astrocytomas, anaplastic astrocytomas, and glioblastomas were 1.9 +/- 0.9, 8.4 +/- 4.0, and 17.1 +/- 7.1% (mean +/- SD), respectively, and their differences were statistically significant (p < 0.05, Student's t test). A trend of inverse relationship between patient survival and the number of tumor cell 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 > or = 25% positive cells, respectively. We conclude, the intriguing correlation between allelic status of D17S795 microsatellite locus and GFAP immunoreactivity suggests the possible involvement of q21.2 segment of chromosome 17 in the morphology and biology of astrocytic tumors.
Muhammad
A K
AK
Department of Neurosurgery, Osaka University Medical School, Japan.
Yoshimine
T
T
Maruno
M
M
Tokiyoshi
K
K
Takemoto
O
O
Ninomiya
H
H
Hayakawa
T
T
D000483:Alleles; D001254:Astrocytoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D001932:Brain Neoplasms / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17; D005909:Glioblastoma / Q000737:chemistry / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D011379:Prognosis