Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non‐small‐cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage

Kim, Taejung; Park, Chan Kwon; Yeo, Chang Dong; Park, Kihoon; Rhee, Chin Kook; Kim, Jusang; Kim, Seung Joon; Lee, Sang Haak; Lee, Kyo‐Young; Yoon, Hyoung‐Kyu

doi:10.1002/jso.23646

Cited by 32 publications

(33 citation statements)

References 32 publications

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“…The incidence of ALK rearrangements was found to be 9.6% (73/763) in NSCLC and 11.0% (54/493) in adenocarcinoma in our study, which was similar to the results previously published in Chinese (Shan et al, 2014;Wang et al, 2014a;Yang et al, 2014) and Asian cohorts (Kim et al, 2014). As previously reported, patients who were ALK-positive were predominantly young women and never/light smokers (Lynch et al, 2004;Rodig et al, 2009;Shaw et al, 2009;Wong et al, 2009;Jokoji et al, 2010;Takahashi et al, 2010;Zhang et al, 2013;Zhang et al, 2014).…”

Section: Discussionsupporting

confidence: 92%

“…The incidence rate of EGFR mutations in our study was similar to those of other studies evaluating cohorts of Asian ethnicity (Pao et al, 2004;Kim et al, 2014;Wang et al, 2014b). Previous results have indicated that the frequency of EGFR mutation was increased in patients with adenocarcinoma, young women, and never smokers (Lynch et al, 2004;Shaw et al, 2009;Li et al, 2013;Wang et al, 2014b).…”

Section: Discussionsupporting

confidence: 91%

“…The deletion in exon 19 and the L858R substitution in exon 21 constitute the most frequent mutations. Tumors expressing one of these mutations are known to show good response to TKIs (Pao et al, 2004;Kim et al, 2014). Two or more concomitant sites of EGFR mutations have also been detected despite the low patient number.…”

Section: Discussionmentioning

confidence: 99%

“…The EGFR mutations are always associated with good responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) (Pao et al, 2004;Kim et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Lei

Wang

et al. 2015

Genet. Mol. Res.

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ABSTRACT. Echinoderm microtubule associated protein like 4-anaplastic lymphoma kinase (EML4-ALK) gene rearrangements and epidermal growth factor receptor (EGFR) mutations in non-small cell lung cancer (NSCLC) have been intensively studied. The objective of this study was to determine the clinicopathological characteristics in genotype-specific subsets of patients with NSCLC to help ensure the optimal identification of patients whose tumors harbor these two driver mutations. The incidence of ALK rearrangements was investigated in 763 NSCLC specimens by immunohistochemistry using a D5F3 antibody, and EGFR mutations were assessed by amplification refractory mutation system (ARMS) in 222 patients with lung adenocarcinoma. Of these, 73 (9.6%) were detected as being ALK-positive; this designation was associated with young age, female gender, never-smokers, lymph node metastasis, and poor tumor differentiation, but not with histology. EGFR mutations were identified in 102 (45.9%) of 222 adenocarcinoma samples, and were more frequent in females and never-smokers. No difference in age was observed. Specifically, we identified several cases of complex EGFR mutations, and concomitant EGFR mutations and ALK rearrangements. These results suggest that young women and never-smokers are at risk for ALK rearrangement. We also identified concomitant mutations of EGFR and rearrangements of ALK in this study.

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Section: Discussionsupporting

confidence: 92%

Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

“…The EGFR mutations are always associated with good responses to EGFR tyrosine kinase inhibitors (EGFR-TKIs) (Pao et al, 2004;Kim et al, 2014).…”

Section: Introductionmentioning

confidence: 99%

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Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Lei

Wang

et al. 2015

Genet. Mol. Res.

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“…Anaplastic lymphoma kinase (ALK)-rearranged non-small cell lung cancer (NSCLC) behaves more aggressively than other NSCLCs, showing early metastasis and an advanced stage at time of diagnosis (1)(2)(3). Similarly, patients with ALK-rearranged NSCLC and high expression of ALK are more likely to be in advanced stages and have worse 2-year progression-free survival rates (4).…”

Section: Introductionmentioning

confidence: 99%

Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC

Noh

Sohn

Song

et al. 2018

Clinical Cancer Research

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Purpose: Anaplastic lymphoma kinase (ALK)-positive cancers are sensitive to small-molecule ALK kinase inhibitors, but most cases experience failure following treatment. Hence, additional drug targets and combination therapeutic treatments are needed. We investigated gene expression that is regulated by the expression of ALK and explored its roles in cancer progression and therapeutic implication. Experimental Design: We screened ALK-rearranged non–small cell lung cancer (NSCLC) cases using immunohistochemistry and fluorescence in situ hybridization and then conducted multiplex gene expression analysis. We also performed a clinicopathologic analysis to validate the findings. Additional cellular experiments, including inhibition and migration assays, and in vivo lung cancer model studies were performed. Results: Among patients with ALK-rearranged NSCLC, integrin β3 (ITGB3) was one of the overexpressed genes in comparison with that in ALK-negative NSCLC (P = 0.0003). ALK and integrin β3 expression were positively correlated, and we discovered that high integrin β3 mRNA expression was associated with metastasis and more advanced tumor stages (P < 0.005; P < 0.05). Furthermore, we found that inhibition of both ALK and integrin β3 led to increased drug sensitivity in vitro and in vivo (both P < 0.05). Conclusions: We discovered a positive correlation between ALK and integrin β3 expression levels in ALK-rearranged NSCLC. Our findings suggest that high integrin β3 expression in ALK-rearranged NSCLC is associated with tumor progression and a worse prognosis. This finding demonstrates the prognostic value of integrin β3 and provides a rationale for combination treatment with ALK and integrin β3 inhibitors in patients with ALK-rearranged NSCLC. Clin Cancer Res; 24(17); 4162–74. ©2018 AACR.

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Correlation between combining 18F–FDG PET/CT metabolic parameters and other clinical features and ALK or ROS1 fusion in patients with non-small-cell lung cancer

Ruan

Liu

Wang

et al. 2020

Eur J Nucl Med Mol Imaging

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Simultaneous diagnostic platform of genotyping EGFR, KRAS, and ALK in 510 Korean patients with non‐small‐cell lung cancer highlights significantly higher ALK rearrangement rate in advanced stage

Cited by 32 publications

References 32 publications

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Clinical characteristics of patients with non-small cell lung cancers harboring anaplastic lymphoma kinase rearrangements and primary lung adenocarcinoma harboring epidermal growth factor receptor mutations

Integrin β3 Inhibition Enhances the Antitumor Activity of ALK Inhibitor in ALK-Rearranged NSCLC

Correlation between combining 18F–FDG PET/CT metabolic parameters and other clinical features and ALK or ROS1 fusion in patients with non-small-cell lung cancer

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