Abstract
BACKGROUND: Distinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same. Since genomic instability is a common feature of cancer, we hypothesized that independently arising neoplasms in an individual patient would exhibit measurable genomic variation, enabling discrimination of tumor lineage and relatedness. The feasibility of analyzing genomic instability expression profiles to distinguish multiple primary lung cancers from metastatic tumors was evaluated. METHODS: This study enrolled 13 patients, with multiple primary lung cancers demonstrating with the histology, who underwent surgery between April 2003 and December 2012 at the Department of the Thoracic Surgery at West China Hospital in Sichuan province of China and 10 patients who were diagnosed as metastasis disease during the same period for comparison purposes. Genomic DNA from lung cancers from individual patients was analyzed by six microsatellites (D2S1363, D6S1056, D7S1824, D10S1239, D15S822, and D22S689) with PCR to identify discordant allelic variation. The experiments were approved by the West China Hospital Ethics committee (No.2013 (33)) and all patients agreed to participate in the study and signed an informed consent form. RESULTS: All of the 10 patients with distant metastasis showed a consistent consequence that we called "unique trend" between primary tumor and distant metastasis. The "trend" is representive in this study, which means that all alleles corresponding to six microsatellite markers were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors. In the group of synchronous lung tumor with different histological types, the result showed a "contradictory trend". Some alleles were detected in DNA from primary tumors but were reduced or not observed in DNA from metastatic tumors and other alleles corresponding to six microsatellite markers were detected in DNA from metastatic tumors but were reduced or not observed in DNA from primary tumors. In the third group (synchronous lung tumor with same histological types), 2 of 8 patients showed "unique trend" and the others showed "contradictory trend". CONCLUSIONS: With polymorphic microsatellite markers, the "unique trend" that represents metastasis cancers and the "contradictory trend" that represents primary multiple tumors are useful in the diagnosis between tumors found at the same time in the pulmonary even diagnosed with the histopathological evaluation from a single patient.