Discrimination of double primary lung cancer from intrapulmonary metastasis by p53 gene mutation

Abstract

Summary When multiple synchronous lung tumours are identified, discrimination of multicentric lung cancers from intrapulmonary metastases by clinical findings is often difficult. We used genetic alterations in p53 gene as a discrimination marker of double primary lung cancers from single lung cancer with intrapulmonary metastasis. Twenty of 861 patients with primary lung cancer who underwent lung resection were selected as subjects because they showed synchronous double solid tumours of the same histological type in the unilateral lung without distant metastases. In addition, they had been diagnosed as lung carcinoma with intrapulmonary metastasis by clinical and histological findings. DNAs were extracted from paraffin-embedded tissue of paired tumours from these 20 patients. Exons 5-9 of the p53 gene were examined for genetic alterations in the tumours by polymerase chain reaction, single-strand conformation polymorphism analysis and subsequent DNA sequencing analysis. Three different patterns in the distribution of p53 mutations in double lung tumours were observed: [A] mutation in only one of the tumours (four cases), [B] different mutations in the tumours (two cases), and [C] same mutation in both tumours (one case). The cases of [A] or [B] patterns could be classified as double primary lung cancers, while the case of the [C] pattern was suggested to be lung cancer with intrapulmonary metastasis. These results suggested that the multicentric cancers were more frequent than the intrapulmonary metastatic cancers in double cancer cases.

The significance of intrapulmonary metastasis in non-small cell lung cancer: upstaging or downstaging? A re-appraisal for the next TNM staging system☆

“…The differentiation between synchronous multiple primary NSCLC and PM is difficult. The criteria proposed by Martini and Melamed in 1975 [1] are still the most widely used by pathologists, although there have been some experimental trials for the discrimination of multiple primary lung cancer from PM using immunohistochemistry or molecular biology [10][11][12][13].…”

Molecular profiling of primary and metastatic neoplasms in the lung using cytologic material obtained by fine‐needle aspiration: Report of two cases

“…18 Nonetheless, mutations involving specific markers such as cerbB2 (Her2Neu) and p53 are useful in the comparison of primary and metastatic neoplasms. Mutations involving these sites are thought to occur early in the neoplastic process in the case of p53 5,19 and are conserved due to conferred growth advantage in the case of c-erbB2. 15 Additional work is necessary to further define the roles that these mutations play in the neoplastic process: which mutations are conserved and which participate in greater clonal diversity in a particular tumor.…”

Synchronous multiple primary lung cancers with different response to gefitinib

“…Matsuzoe et al reported that p53 gene mutation could be used as a clonal marker for the differential diagnosis of multiple cancers because p53 mutation usually precedes metastasis and is conserved in metastases [4][5][6]. However, detection of p53 mutation may not be informative in some patients because it would not be found in all cases and it could develop simultaneously in multiple tumors.…”

“…The relationship between smoking and BAC has been the subject of debate. A higher proportion of patients with BAC Matsuzoe et al [4] p53 mutation 20 (S) Shimizu et al [8] p53 mutation and LOH…”