SYNCHRONOUS AND METACHRONOUS LUNG CARCINOMAS - MOLECULAR EVIDENCE FORMULTICENTRICITY

The present study is aimed to evaluate the genetic evidence for multic entricity of synchronous and metachronous multiple lung carcinomas. Ni neteen cases of synchronous multiple lung carcinomas and 11 cases of m etachronous multiple lung carcinomas were analyzed for p53 protein ove rexpression by immunohistochemistry (DO-7) and for genetic abnormality of the p53 gene by loss of heterozygosity (LOH) at chromosome 17p and by polymerase chain reaction (PCR)-single-strand conformation polymor phism (SSCP) analysis. They were also analyzed for K-ras mutation. DNA from three patients was also sequenced by the dideoxy sequencing meth od to confirm the presence of mutations and determine the base substit utions. Different spectrums of genetic changes, which were evaluated b y a combination of p53 mutation, LOH at chromosome 17p and p53 overexp ression, were observed in 11 of 19 cases of synchronous multiple lung carcinomas (57.9%) in the present study. Similarly, five of 11 cases o f metachronous multiple lung carcinomas (45.4%) showed a different pat tern of genetic changes. The present data suggest that some of the mul tiple carcinomas have different clonal origins, although their histolo gical types are identical, and support the use of genetic markers in t he differential diagnosis between metastasis and second primary carcin oma of the lung.