Perry A, Anderl K, Borell T J, Kimmel D W, Wang C H, O'Fallon J R, Feuerstein B G, Scheithauer B W, Jenkins R B
Division of Neuropathology, Washington University, St Louis, Missouri, USA.
Am J Clin Pathol. 1999 Dec;112(6):801-9. doi: 10.1093/ajcp/112.6.801.
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 one age, grade, and oligodendroglial histology are taken into account.
p53基因失活是星形细胞瘤发生过程中常见的早期事件。另外，由于p16、视网膜母细胞瘤（RB）和CDK4基因与恶性进展有关，检测这些基因在胶质瘤中的缺失或扩增在诊断、预后及治疗方面可能具有重要意义。我们从96例弥漫性胶质瘤和10例非肿瘤标本中获取涂片标本。使用针对CEN9/p16、CEN8/RB、CEN17/p53和CEN12/CDK4的配对探针进行双色荧光原位杂交，结果显示除p53缺失频率较低（7%）外，其他异常频率符合预期。后者支持p53失活通常通过有丝分裂重组发生的观点。检测到的p16/RB/CDK4通路异常与星形细胞分化高度相关，单因素分析显示与患者生存率降低相关。然而，多因素分析中只有患者年龄和组织学分类具有统计学意义。我们得出结论，在弥漫性胶质瘤中，p16/RB/CDK4异常是星形细胞表型的标志物。因此，在形态学特征不明确的病例中，通过荧光原位杂交检测这些异常可能具有诊断价值。尽管我们的样本量较小，但在考虑年龄、分级和少突胶质细胞组织学的情况下，我们发现这些基因异常并无额外的预后意义。
