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Updated: Feb 27, 2026
Next Generation Sequencing for the Detection of Actionable Mutations in Solid and Liquid Tumors
Published on: September 20, 2016
Use of Oncogenic Driver Mutations in Staging of Multiple Primary Lung Carcinomas: A Single-Center Experience
Ramsey Asmar1, Joshua R Sonett2, Gopal Singh2
1Department of Medicine, Columbia University Medical Center, New York, New York.
Objective:
The staging of multiple pulmonary adenocarcinomas requires the distinction of intrapulmonary metastasis (IPM) from multiple primary lung cancers (MPLCs). This can be challenging in some patients, and the addition of data from oncogenic driver mutations in these tumors may be helpful in this determination.
Methods:
As a proof of principle, molecular driver results from primary tumors and their metastases in 45 patients were compared (cohort 1). Then, 69 patients with a total of 154 synchronous or metachronous lung carcinomas were identified, and the pathologic findings were compared with oncogenic driver mutation. Each patient was assigned a highest potential T or M category on the basis of clinical, histopathologic, and molecular findings (cohort 2).
Results:
The concordance rate of EGFR, KRAS, BRAF, and ALK receptor tyrosine kinase gene (ALK) mutations was 96% in cohort 1. In cohort 2, 36% of multiple same-lobe nodules were MPLCs, 40% were IPM, and 24% were noninformative by molecular findings. Of nodules with multiple lobe involvement, 81.5% were MPLCs and 7.4% were IPM, with 11% noninformative. Of metachronous tumors, 52.9% were MPLCs. Overall survival was 100% at 2 years, 95% at 3 years, and 80% at 4 years in patients with available follow-up.
Conclusions:
Oncogenic driver mutations are concordant between primary tumors and metastasis. The largest proportion of MPLCs was seen in tumors of multiple lobes, but with a substantial proportion of MPLCs among single-lobe nodules and with metachronous tumors. Overall survival was higher than expected for the respective highest T or M category, which is in support of the high frequency of MPLC.
