Clinicopathological parameters for circulating tumor DNA shedding in surgically resected non-small cell lung cancer with EGFR or KRAS mutation

• Published in: PloS one Vol. 15; no. 3; p. e0230622
• Main Authors: Cho, Min-Sun, Park, Chul Hwan, Lee, Sungsoo, Park, Heae Surng
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 20.03.2020; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Analysis; Biology and Life Sciences; Biomarkers; Blood; Cancer genetics; Cancer metastasis; Deoxyribonucleic acid; Diagnostic tests; DNA; EDTA; Epidermal growth factor receptors; Formaldehyde; Gene banks; Genetic aspects; Hospitals; K-Ras protein; Lung cancer; Lung diseases; Medical schools; Medicine; Medicine and Health Sciences; Metastases; Mitosis; Morphology; Mutants; Mutation; Necrosis; Non-small cell lung cancer; Non-small cell lung carcinoma; Nucleic acids; Osimertinib; Paraffin; Paraffins; Pathology; Peptides; Peripheral blood; Plasma; Shedding; Small cell lung cancer; Small cell lung carcinoma; Subgroups; Surgery; Tissues; Tumor cells; Tumors; Volumetric analysis; United States > US; South Korea; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0230622

Circulating tumor DNA (ctDNA) is cell-free DNA that is released into peripheral blood by tumor cells. ctDNA harbors somatic mutations and mutant ctDNA obtained from blood can be used as a biomarker in advanced non-small cell lung cancer (NSCLC). In this study, we investigated the clinicopathological properties of tumors that shed ctDNA in surgically resected NSCLC patients. Consecutive cases of NSCLC with matching surgically resected tissue specimens and peripheral or specimen blood samples were eligible for this study. EGFR and KRAS mutations in plasma ctDNA and formalin-fixed paraffin-embedded tissue were analyzed using peptide nucleic acid clamping-assisted method. The plasma and tissue results were compared according to clinicopathological features. Mutation analyses were available for 36 cases. EGFR and KRAS mutations were present in 41.7% (15/36) and 16.7% (6/36) of tissue samples, respectively. Among EGFR and KRAS-mutant tumors, plasma mutation detection sensitivity was 13.3% (2/15) for EGFR and 33.3% (2/6) for KRAS. The presence of ctDNA in plasma was significantly associated with higher pathological tumor stage (p = 0.028), nodal metastasis (p = 0.016), solid adenocarcinoma pattern (p = 0.003), tumor necrosis (p = 0.012), larger primary tumor diameter (p = 0.002) or volume (p = 0.002), and frequent mitosis (p = 0.018) in tissue specimens. All tumors larger than 4 cm in maximal diameter or 25 cm3 in volume shed ctDNA in plasma. In subgroup analysis among EGFR mutated adenocarcinoma, ctDNA was significantly associated with nodal metastasis (p = 0.029), vascular invasion (p = 0.029), solid adenocarcinoma pattern (p = 0.010), and tumor necrosis (p = 0.010), high mitotic rate (p = 0.009), large pathological tumor size (p = 0.027), and large tumor volume on CT (p = 0.027). We suggest that primary or total tumor burden, solid adenocarcinoma morphology, tumor necrosis, and frequent mitosis could predict ctDNA shedding in pulmonary adenocarcinoma.