P53 IMMUNOSTAINING POSITIVITY IS ASSOCIATED WITH REDUCED SURVIVAL AND IS IMPERFECTLY CORRELATED WITH GENE-MUTATIONS IN RESECTED NONSMALL CELL LUNG-CANCER - A PRELIMINARY-REPORT OF LCSG-871
P53 IMMUNOSTAINING POSITIVITY IS ASSOCIATED WITH REDUCED SURVIVAL AND IS IMPERFECTLY CORRELATED WITH GENE-MUTATIONS IN RESECTED NONSMALL CELL LUNG-CANCER - A PRELIMINARY-REPORT OF LCSG-871
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DOI：
10.1378/chest.106.6.377s
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发表时间：
1994-12-01
期刊：
影响因子：
9.6
通讯作者：
MINNA, J
中科院分区：
文献类型：
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作者：
CARBONE, DP;MITSUDOMI, T;MINNA, J
我们调查了 85 名非小细胞肺癌 (NSCLC) 患者的 p53 异常与生存的相关性，这些患者作为肺癌研究组 (LCSG) 871 的一部分接受了根治性切除术。我们之前的研究表明，肺癌中只有一部分 p53 突变会导致过度表达。此外，已经描述了在没有突变的情况下蛋白质过度表达。因此，我们在这组切除的肿瘤标本中测定了p53蛋白过度表达（通过免疫染色）以及p53和ras基因突变（通过单链构象多态性和DNA测序）。 75例有临床随访数据。在所研究的患者中，64% 的患者表现出 p53 过度表达，51% 的患者有 p53 序列突变；然而，一致率仅为67%。在这组患者中，生存率与 p53 免疫染色阳性呈负相关（p=0.05），但与基因突变的存在无关（p=0.62）。通过免疫染色确定的 p53 蛋白过度表达可能会导致不良结果，因为 p53 能够充当显性癌基因，或者，过度表达可能反映肿瘤中持续的 DNA 损伤，作为更具攻击性行为的标志。然而，当通过多变量分析调整阶段、年龄和性别时，p53 过度表达对生存没有独立影响。
We investigated the correlation of p53 abnormalities with survival in 85 patients with non-small cell lung cancer (NSCLC) who had undergone resection with curative intent as part of Lung Cancer Study Group (LCSG) 871. Our previous studies showed that only a subset of p53 mutations in lung cancers result in overexpression. In addition, protein overexpression has been described in the absence of mutation. Therefore, we determined both p53 protein overexpression (by immunostaining) and p53 and ras gene mutations (by single-strand conformation polymorphism and DNA sequencing) in this set of resected tumor specimens. Clinical follow-up data were available for 75 cases. Of the studied patients, 64% showed p53 overexpression and 51% had mutant p53 sequences; however, the concordance rate was only 67%. There was a negative survival correlation with positive p53 immunostaining (p=0.05), but not with the presence of gene mutations (p=0.62) in this group of patients. Overexpression of p53 protein determined by immunostaining may contribute to adverse outcome due to the ability of p53 to act as a dominant oncogene, or alternatively, overexpression may reflect ongoing DNA damage in the tumor as a marker for a more aggressive behavior. When adjusted for stage, age, and gender by multivariate analysis, however, there was no independent impact of p53 overexpression on survival.