Mutations changing the p53 coding sequence were found in 14 of 30 tumor samples (47%), while G:C to T:A transversions which are uncommon in other cancers such as colon cancer were the most frequently observed mutations, in agreement with an earlier report on non-small cell lung cancer in American patients.
However, p53 gene mutations in NSCLC cell lines with ras mutations tended to cluster in exon 8, suggesting the presence of a functional domain of the p53 gene relating to interaction with the ras gene.
In the sera of 13% of the patients (4 of 40 small cell lung cancer and 2 of 6 non-small cell lung cancer) we found antibodies specific for the p53 tumor suppressor gene product.
Our study indicates that there might be an association between accumulation of p53 protein and c-myc over-expression in non-small-cell lung cancer, and that this in particular might apply to adenocarcinomas.
We investigated the immunocytochemical staining and immunoblotting characteristics of 33 different p53 mutant proteins identified in lung cancer cell lines (18 small-cell lung cancer and 15 non-small-cell lung cancer) using monoclonal antibodies pAbs 240, 421 and 1801.
Mutations changing the p53 coding sequence were found in 11 of 15 patients (73.3%) and showed a similar but distinct nucleotide substitution pattern compared with NSCLC, suggesting that a different mutagenic process is involved.
Abnormally sized p53 mRNAs found in a small cell and a non-small cell lung cancer cell line were characterized by sequence analysis of cDNA/PCR products, the RNase protection assay and immunoprecipitation.
CEA, TPA, SCC-Ag, CYFRA 21-1, ferritin, CA19-9, CA50, CA242, H-K-N-ras mutations and p53 mutation seem to be the most prolific in NSCLC, while NSE, BN/GRP, CK-BB, NCAM, IL-2R, IGF-I, transferrin, ANP, mAb (cluster 5), Le-y and c-N-L-myc mutation are markers in SCLC patients.
All of the tumors having mdm2 abnormalities belonged to a subset of NSCLC characterized by a strong accumulation of the p53 protein in the absence of p53 gene mutations.
Counter to previous studies in other solid tumors, immunocytochemical detection of p53 expression does not predict a poor clinical outcome in non-small-cell lung cancer.
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.
No correlation was found between p53 mutations and myc activation in SCLC or in NSCLC, but their association was significantly more frequent in NSCLC than in SCLC.
We performed immunohistochemical staining for mutated p53 using two monoclonal antibodies, PAb1801 and PAb240, in fresh tumour specimens from 103 consecutive patients who underwent surgery for resectable NSCLC.
Putative mutation of the p53 gene (also known as TP53) has also been found to occur frequently in stage I and II NSCLCs and to be associated with more aggressive disease and a poorer prognosis.