Comparative analysis of p53 gene mutations and protein accumulation in human non-small-cell lung cancer.
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.
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Division of Experimental Therapy, The Netherlands Cancer Institute/Antoni van Leeuwenhoek Huis, Amsterdam.
Mooi
W J
WJ
Klaver
S G
SG
Boerrigter
L
L
Wisman
P
P
Elbers
H R
HR
Visser
S
S
Rodenhuis
S
S
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D002289:Carcinoma, Non-Small-Cell Lung / Q000737:chemistry* / Q000235:genetics*; D004591:Electrophoresis, Polyacrylamide Gel; D005091:Exons; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016158:Genes, p53 / Q000235:genetics*; D011905:Genes, ras; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000737:chemistry* / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation; D016133:Polymerase Chain Reaction; D016019:Survival Analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis* / Q000235:genetics
D016159:Tumor Suppressor Protein p53