Thus, mutant p53 genes have been found in urine from patients with bladder cancer, mutant ras genes in stools from patients with colorectal and pancreatic cancers, and both mutant p53 and ras genes in sputum from patients with lung cancer.
The ability of this adenovirus construct (Ad-CMV-p53) to express p53 protein was examined by Western blot analysis in the H358 lung cancer cell line, which has a homozygous deletion of the p53 gene.
A sensitive ELISA to detect serum p53 antibodies was developed and used to examine sera from 186 patients undergoing pulmonary surgery for a suspected lung cancer.
Although the short arm of chromosome 17, which contains the p53 gene, is frequently affected by loss of heterozygosity (LOH) in lung cancer, little is known about similar changes on the long arm.
These results suggest that (1) the K-ras and p53 gene alterations would have no special roles in terms of the lung carcinogenesis in young adults; (2) a positive relationship between smoking and p53 gene alteration would exist in young adults with lung cancer, and (3) K-ras gene alteration would become a prognostic factor in lung cancer.
Because the prognostic relevance of p53 immunostaining in lung cancer is still under debate, we studied the expression pattern and clinical significance of such staining in 73 patients with operable non-small-cell lung cancer. p53 expression was detected on frozen sections with the use of monoclonal antibody p1801, which recognizes both the wild-type and mutant gene product (alkaline phosphatase-anti-alkaline phosphatase method).
We propose that inactivation of both p53 and Rb genes may promote cell divisions causing telomere shortening in lung cancer as in the two-stage model, while there may be another pathway to overcome both M1 and M2 mechanisms, especially for adenocarcinoma.
Furthermore, an observed association between abnormal p53 expression and the patients' smoking history suggests that the p53 gene could be a common target of tobacco-associated carcinogenesis in lung cancer.
To investigate possible correlation between p53 gene alteration and the unique characteristics of lung cancer here, p53 gene status of 36 patients with primary, resected non-small-cell lung cancer (NSCLC) was studied by directly sequencing the cDNA of the p53 gene, then acquiring clinical and pathologic data to correlate p53 gene status with clinical parameters and pathologic staging.
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.
The typical p53 mutations in lung cancer, G to T transversions and G to A and C to T transitions, associated with smoking, accounted for 46% of the mutations detected.
These results indicate that the p53-positive immunophenotype uncovers the occurrence of p53 point mutations in lung cancer and that p53 and c-myc gene alterations are important but represent independent occurrences in the development of lung tumors.
Because the p53 recessive oncogene is mutated and anti-p53 antibodies frequently occur in cancer patients, we wondered if the development of anti-HuD antibodies signaled the presence of HuD mutations in lung cancer.
The wild-type form of p53 is dominant over the mutant; thus, restoration of wild-type p53 function in lung cancer cells may suppress their growth as tumors.
When we analyzed the HLA subtype of lung cancer cell lines with known p53 missense mutations, we found that all of the mutant oncopeptides predicted to be presentable by HLA A*0201 came from tumors that either did not carry the A*0201 allele or had lost that allele in the process of tumorigenesis.
In contrast to the previous report of biallelic expression of p53 in a case with a germline missense mutation, preferential expression of the wild-type allele was observed in the heterozygous state in both normal lung and peripheral blood lymphocytes of our case, whereas expression of mutant mRNA was readily detectable in her lung cancer in the absence of the remaining wild-type allele.
Because of evidence that the nature and site of p53 mutations reflect not only the mutagens involved in tumorigenesis but also the capacity for malignant transformation, the characterization of mutations of the p53 gene may provide a basis for assessing further risk factors, as well as for estimating prognosis in patients with lung cancer.
Our data suggest that point mutations of the p53 gene are infrequent in pulmonary carcinoids thus contrasting the findings in other histological types of lung cancer, in particular small-cell lung cancer.