PROGNOSTIC IMPLICATIONS OF P53 OVEREXPRESSION IN SUPRATENTORIAL ASTROCYTIC TUMORS
PROGNOSTIC IMPLICATIONS OF P53 OVEREXPRESSION IN SUPRATENTORIAL ASTROCYTIC TUMORS
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DOI：
10.1227/00006123-199411000-00005
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发表时间：
1994-11-01
期刊：
影响因子：
4.8
通讯作者：
FINCH, PW
中科院分区：
文献类型：
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作者：
CHOZICK, BS;PEZZULLO, JC;FINCH, PW
野生型p53基因被认为在肿瘤抑制中发挥关键作用，并已被证明在体外逆转肿瘤细胞的转化表型。P53活性的这一方面的突变失活在许多人类肿瘤中经常发生，包括星形细胞瘤，被认为是肿瘤进展的关键步骤。我们以前已经发现，P53免疫反应的存在与发生在年轻患者中的恶性星形细胞瘤显著相关，尽管在老年患者的肿瘤中很少发生。鉴于年轻年龄是预测星形细胞瘤患者较长生存期的最一致的临床因素，这表明P53蛋白积累可能是一个提高生存期的分子预测因子。为了验证这一假设，我们回顾研究了149例星形细胞瘤患者P53过度表达与生存的关系，采用单变量和多变量分析来确定其在预测生存中的价值。尽管我们的分析重申了年轻与生存率增加之间的密切联系，但我们无法证明有P53免疫反应的III级和IV级肿瘤患者与无P53免疫反应的患者相比，在生存率上有任何差异。据推测，一旦肿瘤进展到高级别，P53状态作为生存预测指标的相对重要性就很低，可能是因为与恶性肿瘤相关的大量累积的基因改变。相反，从生存曲线上看，在II级星形细胞瘤中存在P53过表达似乎表明与没有P53免疫反应的患者相比，生存时间更短。但在多变量分析中，该变量作为独立预测变量未达到统计学意义(P=0.08)。这可能是因为研究的II级肿瘤患者的人数相对较少(n=24)。然而，有组织学证据的恶变患者的P53染色水平显著高于那些没有进展证据的患者。这些数据与P53在恶性进展过程中驱动一种主要细胞类型克隆性增殖的可能作用是一致的，并提示P53过表达可能被证明是II级星形细胞瘤患者预后的分子标志物。
THE WILD-TYPE p53 gene is thought to play a critical role in tumor suppression and has been shown to reverse the transformed phenotype of tumor cells in vitro. Mutational inactivation of this aspect of p53 activity occurs frequently in many human neoplasms, including astrocytomas, and is thought to represent a critical step in tumor progression. We have found previously that the presence of p53 immunoreactivity was significantly associated with malignant astrocytomas arising in younger patients, although occurring infrequently in tumors in older patients. Given that young age is the most consistent clinical factor predictive of longer survival in patients with astrocytomas, this suggested that p53 protein accumulation might be a molecular predictor of enhanced survival. To test this hypothesis, we retrospectively studied the association of p53 overexpression with survival in 149 patients with astrocytomas, using univariate and multivariate analysis to determine its value in predicting survival. Although our analysis reaffirmed the strong association between young age and increased survival, we were unable to demonstrate any difference in survival between patients with Grade III and IV tumors with p53 immunoreactivity compared with those without. Presumably, once a tumor has progressed to high grade, the relative importance of p53 status as a predictor of survival is low, probably because of the large number of accumulated genetic alterations associated with malignant tumors. In contrast, the presence of p53 overexpression in Grade II astrocytomas seemed from survival curves to indicate shorter survival compared with patients who had no p53 immunoreactivity. However, this variable did not quite reach statistical significance (P = 0.08) as an independent predictive variable in multivariate analysis. This may be because of the relatively small population of patients with Grade II tumors that were studied (n = 24). However, patients with histological evidence of malignant degeneration had significantly higher levels of p53 staining than those with no evidence of progression. These data are consistent with the likely role of p53 in driving the clonal expansion of a dominant cell type during malignant progression and suggest that p53 overexpression may prove to be a molecular marker for prognosis in patients with Grade II astrocytomas.