p53 mutation analysis for definite diagnosis of multiple primary lung carcinoma

Cancer. 2002 Jan 1;94(1):188-96. doi: 10.1002/cncr.10001.


Background: The detection of a second tumor in patients with lung carcinoma raises the question whether this lesion is a metastasis or a second primary lung carcinoma. Patients cannot always be categorized satisfactorily according the criteria of multiple lung carcinoma proposed by Martini and Melamed. This may result in an inadequate treatment schedule in individual patients. Because p53 mutations can be used as clonal marker, the authors investigated whether p53 mutation analysis can differentiate between primary lung carcinomas and metastatic disease.

Methods: Sixty-four tumors in 31 patients with synchronous and metachronous lung tumors were investigated by p53 mutation analysis.

Results: In 21 patients, the tumors showed different p53 mutations, and therefore a definite diagnosis of multiple primary lung carcinoma was made. One of these patients did not meet the criteria of Martini and Melamed. In two other patients not matching these criteria, identical mutations were demonstrated in both tumors, indicating the presence of metastatic disease. In eight patients, analysis was not conclusive or possible.

Conclusions: p53 mutation analysis can be a useful tool to confirm or rule out multiple primary lung carcinoma, and the results confirm the criteria of Martini and Melamed. However, in patients not meeting these criteria, the diagnosis of multiple lung carcinoma still has to be considered, and metastatic disease has to be ruled out. P53 mutation analysis can be helpful for this purpose.

MeSH terms

  • Adenocarcinoma / genetics
  • Adenocarcinoma / pathology
  • Adenocarcinoma / secondary
  • Carcinoma, Adenosquamous / genetics
  • Carcinoma, Adenosquamous / pathology
  • Carcinoma, Adenosquamous / secondary
  • Carcinoma, Squamous Cell / genetics
  • Carcinoma, Squamous Cell / pathology
  • Carcinoma, Squamous Cell / secondary
  • DNA, Neoplasm / analysis
  • Genes, p53*
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology*
  • Mutation
  • Neoplasms, Multiple Primary / genetics*
  • Neoplasms, Multiple Primary / pathology*
  • Neoplasms, Second Primary / genetics*
  • Neoplasms, Second Primary / pathology*
  • Polymerase Chain Reaction
  • RNA, Neoplasm / analysis


  • DNA, Neoplasm
  • RNA, Neoplasm