Abstract
In cases of multiple lung cancers, individual tumors may represent either a primary lung cancer or both primary and metastatic lung cancers. Treatment selection varies depending on such features, and this discrimination is critically important in predicting prognosis. The present study was undertaken to determine the efficacy and validity of mutation analysis as a means of determining whether multiple lung cancers are primary or metastatic in nature. The study involved 12 patients who underwent surgery in our department for multiple lung cancers between July 2014 and March 2016. Tumor cells were collected from formalin-fixed paraffin-embedded tissues of the primary lesions by using laser capture microdissection, and targeted sequencing of 53 lung cancer-related genes was performed. In surgically treated patients with multiple lung cancers, the driver mutation profile differed among the individual tumors. Meanwhile, in a case of a solitary lung tumor that appeared after surgery for double primary lung cancers, gene mutation analysis using a bronchoscopic biopsy sample revealed a gene mutation profile consistent with the surgically resected specimen, thus demonstrating that the tumor in this case was metastatic. In cases of multiple lung cancers, the comparison of driver mutation profiles clarifies the clonal origin of the tumors and enables discrimination between primary and metastatic tumors.
Highlights
In cases of synchronous or metachronous multiple cancers, individual tumors may be comprised of either a primary lung cancer or both primary and metastatic lung cancers
We examined 24 surgically resected tumors from 12 patients for targeted sequencing, with their buffy coat samples utilized as normal controls
There was no overlap of mutations among the individual lung cancers detected in any patient
Summary
In cases of synchronous or metachronous multiple cancers, individual tumors may be comprised of either a primary lung cancer or both primary and metastatic lung cancers. There are no specific clinical or radiologic features that can be used to confidently distinguish multiple primary cancers from intrapulmonary metastases in all cases, and the differential diagnosis is at times perplexing in the clinical setting. Their different www.impactjournals.com/oncotarget biological activities may be responsible for prognostic differences, and patients with intrapulmonary metastasis tend to have a poor prognosis. There may be cases in which such an approach is difficult to apply clinically As both a more precise and clinically applicable method, we undertook comprehensive mutation analysis with targeted deep sequencing and evaluated the possibility of identifying the clonality of individual lung cancers by using their mutations as a diagnostic marker. We evaluated the efficacy and broad clinical utility of this novel method from the standpoint of understanding the pathology and selecting the most appropriate treatment
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