Discrimination Between Primary Lung Cancer and Lung Metastases by Genomic Profiling

In cases of lung tumors that occur after treatment for malignancies in other organs, the tumor may represent either a primary lung cancer or a solitary pulmonary metastasis from the other tumor. Because some lung tumors are difficult to differentiate on the basis of imaging and pathologic findings, treatment selection is often difficult. In this study, we attempted to make a genomic diagnosis of primary and metastatic lung tumors by analyzing tumor samples using next-generation sequencing and evaluated the efficacy and validity of the genomic diagnosis.

A total of 24 patients with a solitary lung nodule and a history of other malignancies were enrolled in this study. Tumor cells were selected from tissue samples using laser capture microdissection. DNA was extracted from those cells and subjected to targeted deep sequencing of 53 genes.

The driver mutation profiles of the primary lung tumors were discordant from those of the primary tumors in other sites, whereas the mutation profiles of pulmonary metastases and previous malignancies were concordant. In all 24 patients, we could diagnose either primary lung cancer (six patients) or lung metastases (18 patients) on the basis of whether gene mutation profiles were concordant or discordant. In 12 patients (50.0%), discrepancies were observed between the genomic and clinical or histopathologic diagnoses.

In patients with a solitary lung lesion and a history of cancer, tumor-specific mutations can serve as clonal markers, affording a more accurate understanding of the pathological condition and thus possibly improving both treatment selection and patient outcome.