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Driver Mutation Analysis and PD-L1 Expression in Synchronous Double Primary Lung Cancer

Synchronous double primary lung cancer (SDPLC) is detected more frequently than in the past. However, the genetic features, diagnosis, and outcome are not well known. For diagnostic and management applications, we collected 110 lesions from 55 patients who underwent surgical resection to analyze the 5 known driver mutations (EGFR, KRAS, BRAF, EML4-ALK, and ROS1) and programmed cell death ligand 1 (PD-L1) expression in various histologic types of SDPLC. Among 110 tumor lesions, 55 (50%) tumors were found harboring EGFR mutations. In addition, there were 5 (4.55%) tumors harboring EML4-ALK fusions, and 9 (8.18%) KRAS mutations. Only 1 tumor had the coexistence of L858R mutation and EML4-ALK fusion. No BRAF or ROS1 aberrations could be detected. Combining the results for the mutation and fusion patterns, 4 (7.27%) and 47 (85.5%) patients were assessed as having the same clonality and different clonality, respectively. Strikingly, patients with EGFR mutations classified as having same clonality were commonly observed among patients aged above 65 years old (P=0.021). The frequency of PD-L1 expression was 14.54% (16/110). PD-L1 had higher positive results in male, in squamous cell carcinoma subtype, and in tumors >3 cm in diameter. Univariable analysis revealed that lymph node metastasis, smoking history, and male predict worse replase-free survival and overall survival. EGFR/KRAS mutation and EML4-ALK fusion status evaluation was an important tool to support the diagnosis of SDPLC. Following resection, these marks could be used to guide targeted treatment decisions.