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

ABSTRACT: 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.

SUBMITTER: Cho MS

PROVIDER: S-EPMC7083310 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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

Cho Min-Sun MS Park Chul Hwan CH Lee Sungsoo S Park Heae Surng HS

PloS one 20200320 3

<h4>Background</h4>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.<h4>Methods</h4>Consecutive cases of NSCLC with matching surgically resected tissue specimens and periphe ...[more]

PMID: 32196518

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Project description:BackgroundThe rapid aging of the population in Japan has been accompanied by an increased rate of surgery for lung cancer among elderly patients. It is thus an urgent priority to map out a treatment strategy for elderly patients with primary lung cancer. Although surgical resection remains standard treatment for early stage non-small-cell lung cancer (NSCLC), it is now essential to confirm the status of epidermal growth factor receptor (EGFR) gene mutations when planning treatment strategies. Furthermore, several studies have reported that EGFR mutations are an independent prognostic marker in NSCLC. However, the relations between age group and the molecular and pathological characteristics of NSCLC remain unclear. We studied the status of EGFR mutations in elderly patients with NSCLC and examined the relations of EGFR mutations to clinicopathological factors and outcomes according to age group.MethodsA total of 388 consecutive patients with NSCLC who underwent complete tumor resection in our hospital from 2006 through 2008 were studied retrospectively. Formalin-fixed, paraffin-embedded tissue sections were used to isolate DNA from carcinoma lesions. Mutational analyses of EGFR gene exons 19, 20, and 21 and KRAS gene exons 12 and 13 were performed by loop-hybrid mobility shift assay, a highly sensitive polymerase chain reaction-based method.ResultsEGFR mutations were detected in 185 (47.7%) and KRAS mutations were detected in 33 (8.5%) of the 388 patients. EGFR mutations were found in a significantly higher proportion of patients younger than 80 years (younger group; 178/359, 49.6%) than in patients 80 years or older (older group; 7/29, 24.1%) (P = 0.008). In contrast, KRAS mutations were more common in the older group (6/29, 20.7%) than in the younger group (27/359, 7.5%) (P = 0.014). The older group showed a trend toward a higher rate of 5-year overall survival among elderly patients with EGFR mutations (100%) than among those with wild-type EGFR (66.2%), but the difference was not significant.ConclusionsOur results suggest that the EGFR status of patients with NSCLC differs between patients 80 years or older and those younger than 80 years. EGFR mutation status might be a prognostic marker in elderly patients with completely resected NSCLC.

Project description:BACKGROUND:A number of mutations in key oncogenes have been identified as important for the initiation and maintenance of lung adenocarcinoma (LAC). This study elucidated the prevalence and prognostic significance of mutations in the epidermal growth factor receptor gene (EGFR) and rearrangements in the anaplastic lymphoma kinase gene (ALK) in patients with surgically resected primary LAC. PATIENTS AND METHODS:We retrospectively analyzed 675 consecutive patients who underwent radical resection at a single institution. We concurrently analyzed mutations in EGFR and the Kirsten rat sarcoma viral oncogene homolog gene (KRAS) by reverse transcription (RT)-PCR, and investigated ALK rearrangements by immunohistochemistry. LAC with or without various oncogenic mutations was studied for clinicopathological features and their association with disease-free survival (DFS) and overall survival (OS). RESULT:ALK rearrangements and EGFR mutations were detected in 75 and 312 patients, respectively, with coexistence in 5 cases. ALK rearrangements and mutations in EGFR and KRAS were mutually exclusive. Compared with patients with EGFR mutations, ALK rearrangements were more common in younger patients, and those with advanced tumors, lymph node metastases, and higher rates of postoperative adjuvant therapy. Histologically, EGFR mutations were more common than ALK rearrangements in patients with the acinar predominant subtype and the lepidic predominant subtype of LAC, whereas ALK rearrangements were more frequent in the solid predominant subtype with mucin production and invasive mucinous adenocarcinomas. ALK-positive patients had a significantly worse DFS than those with EGFR mutations and wild-type (WT) patients. The mean OS after surgical procedures was significantly longer in EGFR-mutated versus WT patients. No significant differences were found in patients with ALK-positive tumors compared with EGFR-mutated and WT patients. CONCLUSION:Clinicopathological features of LAC with ALK rearrangements differ from those of LAC with EGFR mutations. Patients with ALK rearrangements had a significantly worse DFS than those harboring EGFR mutations. Thus, ALK rearrangements are an adverse prognostic factor in surgically-resected LAC patients, while EGFR mutations are associated with a better prognosis.

Dataset Information

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

Publications

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

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