Low frequency of p53 and k-ras codon 12 mutations in non-small cell lung carcinoma (NSCLC) tumors and surgical margins

Tumori. 2007 Sep-Oct;93(5):473-7. doi: 10.1177/030089160709300511.

Abstract

Aims and background: Lung cancer is one of the most common cancers and has became a predominant cause of cancer-related death throughout the world. The k-ras codon 12 mutation, which is the most common lung cancer mutation, is found in 15 to 30% of all lung cancers. Furthermore, the p53 gene has a very important role in the biological properties of tumor cells, and it is mutated in about 50% of non-small cell lung cancers. Residual tumor cells remain in surgical margins diagnosed as tumor free by histopathological techniques, and they can play a role in forming any local recurrence. Molecular methods may be exploited that are sensitive enough to detect small numbers of tumor cells.

Methods: In the present study, we examined p53 gene mutations and k-ras codon 12 mutations from the tumor samples and surgical margins of 34 non-small-cell lung cancer patients. P53 gene mutations were analyzed by single strand conformational polymorphism analysis, heterodublex analysis and DNA sequencing. K-ras codon 12 mutations were analyzed by the mutagenic PCR-restricted fragment length polymorphism method.

Results: A p53 mutation was detected only in primary tumors of 3 out of 34 patients (8.82%). These mutations were clustered in exon 5. Moreover, a k-ras codon 12 mutation was detected in both the primary tumor and the surgical margin tissues of 2 out of 34 patients (5.88%).

Conclusions: The detected mutation rate was low, in the range given in the literature. We think that different mechanisms related to other genes and individual genetic differences might play a role in cancer formation in our study group. We believe that molecular studies are necessary to identify biomarkers and to determine genetic alterations in histopathologically normal surgical margins.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / surgery
  • Adult
  • Aged
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Adenosquamous / surgery
  • Carcinoma, Large Cell / genetics
  • Carcinoma, Large Cell / pathology
  • Carcinoma, Large Cell / surgery
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Carcinoma, Non-Small-Cell Lung / surgery
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / surgery
  • Codon / genetics
  • DNA, Neoplasm / genetics
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lung Neoplasms / surgery
  • Male
  • Middle Aged
  • Mutation / genetics*
  • Neoplasm Staging
  • Polymerase Chain Reaction
  • Polymorphism, Single-Stranded Conformational
  • Prognosis
  • Proto-Oncogene Proteins / genetics*
  • Proto-Oncogene Proteins p21(ras)
  • Survival Rate
  • Tumor Suppressor Protein p53 / genetics*
  • ras Proteins / genetics*

Substances

  • Codon
  • DNA, Neoplasm
  • KRAS protein, human
  • Proto-Oncogene Proteins
  • Tumor Suppressor Protein p53
  • Proto-Oncogene Proteins p21(ras)
  • ras Proteins