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

 Min-Sun Cho  ;  Chul Hwan Park  ;  Sungsoo Lee  ;  Heae Surng Park 
 PLOS ONE, Vol.15(3) : e0230622, 2020-03 
Journal Title
Issue Date
Adult ; Aged ; Aged, 80 and over ; Carcinoma, Non-Small-Cell Lung / metabolism ; Carcinoma, Non-Small-Cell Lung / pathology* ; Carcinoma, Non-Small-Cell Lung / surgery ; Circulating Tumor DNA / blood ; Circulating Tumor DNA / metabolism* ; ErbB Receptors / blood ; ErbB Receptors / genetics ; Female ; Humans ; Lung Neoplasms / metabolism ; Lung Neoplasms / pathology* ; Lung Neoplasms / surgery ; Male ; Middle Aged ; Neoplasm Staging ; Polymorphism, Single Nucleotide ; Proto-Oncogene Proteins p21(ras) / blood ; Proto-Oncogene Proteins p21(ras) / genetics*
Background: 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.

Methods: 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.

Results: 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).

Conclusion: We suggest that primary or total tumor burden, solid adenocarcinoma morphology, tumor necrosis, and frequent mitosis could predict ctDNA shedding in pulmonary adenocarcinoma.
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1. College of Medicine (의과대학) > Dept. of Radiology (영상의학교실) > 1. Journal Papers
1. College of Medicine (의과대학) > Dept. of Thoracic and Cardiovascular Surgery (흉부외과학교실) > 1. Journal Papers
Yonsei Authors
Park, Chul Hwan(박철환) ORCID logo https://orcid.org/0000-0002-0004-9475
Lee, Sung Soo(이성수) ORCID logo https://orcid.org/0000-0001-8998-9510
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