COMPARATIVE-ANALYSIS OF P53 GENE-MUTATIONS AND PROTEIN ACCUMULATION IN HUMAN NON-SMALL-CELL LUNG-CANCER

被引:82
作者
TOP, B
MOOI, WJ
KLAVER, SG
BOERRIGTER, L
WISMAN, P
ELBERS, HRJ
VISSER, S
RODENHUIS, S
机构
[1] NETHERLANDS CANC INST, ANTONI VAN LEEUWENHOEK HUIS, DIV EXPTL THERAPY, 1066 CX AMSTERDAM, NETHERLANDS
[2] NETHERLANDS CANC INST, ANTONI VAN LEEUWENHOEK HUIS, DIV PATHOL, AMSTERDAM, NETHERLANDS
[3] NETHERLANDS CANC INST, ANTONI VAN LEEUWENHOEK HUIS, DIV MED ONCOL, AMSTERDAM, NETHERLANDS
[4] ST ANTONIUS HOSP, DEPT PATHOL, NIEUWEGEIN, NETHERLANDS
关键词
D O I
10.1002/ijc.2910640203
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
A series of 54 resected primary non-small-cell lung carcinomas was analyzed for p53 gene mutations and for p53 protein accumulation and the findings were correlated with clinical parameters. Mutations in exons 5 through 8 of the P53 gene were identified by a denaturing gradient gel electrophoresis (DGGE) assay and cycle sequencing, whereas p53 protein accumulation was detected in paraffin-embedded tissue by immunostaining using 2 different murine monoclonal antibodies (MAbs) (BP53-12 and DO7). A p53 gene mutation and/or p53 protein accumulation was found in 37 of 54 tumors. Mis-sense mutations were closely associated with positive immunostaining, which was intense in 15 out of 17 cases with a mutation. In 10 tumors, obvious p53 accumulation was detected in the absence of mutations in exons 5 through 8. Conversely, only one of 8 p53 non-sense mutations led to detectable p53 accumulation. The most frequent single base changes were G --> T transversions and C --> T transitions. The presence of a p53 alteration was not related to age, tumor size, stage or histology. However, we found a significant inverse correlation between p53 alterations and the presence of a K-ras mutation. This was reflected in the overall postoperative survival data: patients with p53 alterations in their tumors tended to have a better prognosis than those without a p53 alteration; however, this difference was lost when cases with a K-ras mutation were omitted from the analysis. (C) 1995 Wiley-Liss, Inc.
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页码:83 / 91
页数:9
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