TY - JOUR
T1 - Detection of p16, RB, CDK4, and p53 gene deletion and amplification by fluorescence in situ hybridization in 96 gliomas
AU - Perry, Arie
AU - Anderl, Kari
AU - Borell, Tom J.
AU - Kimmel, David W.
AU - Wang, Chiao H.
AU - O'Fallon, Judith R.
AU - Feuerstein, Burt G.
AU - Scheithauer, Bernd W.
AU - Jenkins, Robert B.
PY - 1999
Y1 - 1999
N2 - Inactivation of the p53 gene is a common early event of astrocytoma tumorigenesis. Alternatively, since the p16, retinoblastoma (RB), and CDK4 genes have been implicated in malignant progression, detection of losses or amplifications of these genes in gliomas could be diagnostically, prognostically, and therapeutically important. We obtained smear preparations from 96 diffuse gliomas and 10 nonneoplastic specimens. Dual-color fluorescence in situ hybridizations using paired probes for CEN9/p16, CEN8/RB, CEN17/p53, and CEN12/CDK4 were performed and revealed expected frequencies of abnormalities, except for p53 losses, which were low (7%). The latter supports the concept that p53 inactivation usually occurs by mitotic recombination. Detected abnormalities of the p16/RB/CDK4 pathway were highly associated with astrocytic differentiation and were univariately associated with decreased patient survival. However, only patient age and histologic classification retained statistical significance on multivariate analysis. We conclude that in diffuse gliomas, p16/RB/CDK4 abnormalities are markers of astrocytic phenotype. Thus, their detection by fluorescence in situ hybridization may have diagnostic usefulness in cases with equivocal morphologic features. Although our numbers are small, we find no additional prognostic significance to these genetic abnormalities once age, grade, and oligodendroglial histology are taken into account.
AB - Inactivation of the p53 gene is a common early event of astrocytoma tumorigenesis. Alternatively, since the p16, retinoblastoma (RB), and CDK4 genes have been implicated in malignant progression, detection of losses or amplifications of these genes in gliomas could be diagnostically, prognostically, and therapeutically important. We obtained smear preparations from 96 diffuse gliomas and 10 nonneoplastic specimens. Dual-color fluorescence in situ hybridizations using paired probes for CEN9/p16, CEN8/RB, CEN17/p53, and CEN12/CDK4 were performed and revealed expected frequencies of abnormalities, except for p53 losses, which were low (7%). The latter supports the concept that p53 inactivation usually occurs by mitotic recombination. Detected abnormalities of the p16/RB/CDK4 pathway were highly associated with astrocytic differentiation and were univariately associated with decreased patient survival. However, only patient age and histologic classification retained statistical significance on multivariate analysis. We conclude that in diffuse gliomas, p16/RB/CDK4 abnormalities are markers of astrocytic phenotype. Thus, their detection by fluorescence in situ hybridization may have diagnostic usefulness in cases with equivocal morphologic features. Although our numbers are small, we find no additional prognostic significance to these genetic abnormalities once age, grade, and oligodendroglial histology are taken into account.
KW - Astrocytoma
KW - Cyclin-dependent kinases
KW - Fluorescence in situ hybridization
KW - Glioma
KW - Retinoblastoma gene
KW - p16 gene
KW - p53 gene
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U2 - 10.1093/ajcp/112.6.801
DO - 10.1093/ajcp/112.6.801
M3 - Article
C2 - 10587703
AN - SCOPUS:0033491737
SN - 0002-9173
VL - 112
SP - 801
EP - 809
JO - American journal of clinical pathology
JF - American journal of clinical pathology
IS - 6
ER -