Abstract
BackgroundDistinguishing 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.MethodsThis 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.ResultsAll 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”.ConclusionsWith 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.
Highlights
Distinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same
In each case of the synchronous multiple primary lung cancers; the first tumor was designated as Tumor 1 (T1), while subsequent tumors were designated as Tumor 2 (T2)
One objective of the current investigation was to identify microsatellite markers that are useful in the detection of measurable genomic variation among multiple tumor-derived DNAs from individual patients
Summary
Distinguishing between multiple primary lung cancers and metastatic tumors is often difficult when the tumor histology is same. Surgery-based multi-discipline treatment has significantly prolonged the survival for patients with lung cancer, and at the same time increased risk for multiple primary cancers after the first treatment. Diagnostic criteria are based on pathology and radiology, the majority of multiple primary lung cancers are misdiagnosed as metastatic cancer in the issue. When patients develop multiple, morphologically similar lung cancer, the clinical diagnosis becomes critical for the selection of an appropriate treatment (surgery for multiple primary tumors versus systemic chemotherapy for solitary pulmonary metastatic disease). Traditional histopathological assessment of neoplasms of the aerodigestive tract cannot definitively distinguish multiple primary cancers from metastatic disease when solitary, histologically similar cancers arise synchronously or metachronously in an individual patient. Comparison of the histology of both neoplasms for similarity or difference in histologic grade may suggest a common or independent origin, but it is recognized that tumor grade can show regional heterogeneity in an individual neoplasms, and that metastases may not always display the same grades as their parent primaries [8]
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