Mutations of the P53 tumor suppressor gene as clonal marker for multiple primary lung cancers

Second primary lung cancers are prevalent after treatment for initial lung cancer, and the lung is also one of the most frequent sites for recurrence after removal of early-stage lung cancer. The objective of the present study is to clarify the clonal origin of the second tumor with the p53 gene mutation used as a clonal marker.

Of 794 consecutive patients who underwent pulmonary resection for primary lung cancer from 1980 to 1993, 22 required second pulmonary resection during the follow-up period, with a median interval of 38 months. We examined 16 of these patients for mutations of the p53 gene occurring in exons 5 through 8 by the polymerase chain reaction/single strand conformation polymorphism method. Differential diagnosis was also made on a morphologic basis, considering the degree of cellular differentiation and cytologic subtypes.

Nine of the 16 patients analyzed had at least one p53 mutation in their tumors. We were thus able to make molecular diagnoses for these patients. The mutational status of the p53 gene was discordant in all nine patients, suggesting a different clonal origin despite the fact that six of them had almost identical histologic features.

Analysis of p53 gene mutations was thus useful in distinguishing second primary lung cancers from recurrent tumors. The observed heterogeneity of p53 status was also in line with the "field cancerization" concept.