Detecting EGFR mutations and ALK/ROS1 rearrangements in non‐small cell lung cancer using malignant pleural effusion samples

Yao, Yi; Peng, Min; Shen, Qinglin; Hu, Qinyong; Gong, Hongyun; Li, Qingqing; Zheng, Zhaohui; Xu, Bin; Li, Yingge; Dong, Yi

doi:10.1111/1759-7714.12932

Cited by 10 publications

(12 citation statements)

References 24 publications

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“…Cytological specimens have been effectively and reliably used in gene detections for the patients with advanced lung cancer who have no chance of surgery [35]. The technology of ARMS and RTqPCR has the advantages of high sensitivity, simple operation, and short time, but it was previously limited to single-gene detection.…”

Section: Discussionmentioning

confidence: 99%

Multigene Combined Detection by RT-qPCR Using Cytological Specimens

Zhao

et al. 2021

Acta Cytologica

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Objective: The aim of the study was to investigate the mutation status of multiple driver genes by RT-qPCR and their significance in advanced lung adenocarcinoma using cytological specimens. Materials and Methods: 155 cytological specimens that had been diagnosed with lung adenocarcinoma in the Fourth Hospital of Hebei Medical University were selected from April to November 2019. The cytological specimens included serous cavity effusion and fine-needle aspiration biopsies. Among cytological specimens, 108 cases were processed by using the cell block method (CBM), and 47 cases were processed by the disposable membrane cell collector method (MCM) before DNA/RNA extraction. Ten drive genes of EGFR, ALK, ROS1, BRAF, KRAS, NRAS, HER2, RET, PIK3CA, and MET were combined detected at one step by the amplification refractory mutation system and ABI 7500 RT-qPCR. Results: The purity of RNA (p = 0.005) and DNA (p = 0.001) extracted by using the MCM was both significantly higher than that extracted by using the CBM. Forty-seven cases of fresh cell specimens processed by the MCM all succeeded in multigene detections, while of 108 specimens processed by the CBM, 6 cases failed in multigene detections. Among 149 specimens, single-gene mutation rates of EGFR, ALK, ROS1, RET, HER2, MET, KRAS, NRAS, BRAF, and PIK3CA mutations were 57.71%, 6.04%, 3.36%, 2.68%, 2.01%, 2.01%, 1.34%, 0.67%, 0% and 0% respectively, and 6 cases including 2 coexistence mutations. We found that mutation status was correlated with gender (p = 0.047), but not correlated with age (p = 0.141) and smoking status (p = 0.083). We found that the EGFR mutation status was correlated with gender (p = 0.003), age (p = 0.015) and smoking habits (p = 0.007), and ALK mutation status was correlated with age (p = 0.002). Conclusion: Compared with the CBM, the MCM can improve the efficiency of DNA/RNA extraction and PCR amplification by removing impurities and enriching tumor cells. And we speculate that the successful detection rate of fresh cytological specimens was higher than that of paraffin-embedded specimens. EGFR, ALK, and ROS1 mutations were the main driver mutations in patients with advanced lung adenocarcinoma. We speculate that EGFR and ALK are more prone to concomitant mutations, respectively. Targeted therapies for patients with coexisting mutations need further study.

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Section: Discussionmentioning

confidence: 99%

Multigene Combined Detection by RT-qPCR Using Cytological Specimens

Zhao

et al. 2021

Acta Cytologica

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“…The low abundance of mutated genes and the high sensitivity of ARMS-PCR may account for the fact that only one T790M mutation was not found by NGS, Some reports have demonstrated the diagnostic accuracy of MPE and tumor tissue for the detection of oncogenic driver genes. 22,26,27 T A B L E 2 Oncogenic driver gene mutation status in MPE cell block specimen. However, there are almost no reports regarding the efficacy of TKIs targeting mutations detected solely in MPEs.…”

Section: Progression-free Survival and Overall Survivalmentioning

confidence: 99%

“…Several technologies have been developed for detecting common oncogenic driver genes in MPE cell blocks, including Sanger sequencing, amplification refractory mutation system polymerase chain reaction (ARMS‐PCR), fluorescence in situ hybridization, and next‐generation sequencing (NGS). The above methods used for common oncogenic driver gene detection achieved a sensitivity of 53%–95%, specificity of 64%–100%, and concordance of 79%–100% in tumor tissue 22–24,26,27 . However, more detailed clinical validation is required to evaluate the clinical application of MPE, especially their predictive significance.…”

Section: Introductionmentioning

confidence: 99%

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Role of molecular testing for malignant pleural effusion in targeted therapy for advanced non‐small cell lung cancer

Lin

et al. 2023

Diagnostic Cytopathology

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Objectives To confirm the predictive value of targeted therapies for oncogenic driver gene mutations detected in malignant pleural effusion (MPE) cell blocks from patients with advanced non‐small cell lung cancer (NSCLC). Methods For patients with NSCLC whose tumor tissues could not be used to detect oncogenic driver gene status, molecular mutation status in 101 MPE cell blocks was tested using amplification refractory mutation system polymerase chain reaction prior to treatment. Corresponding targeted therapies were adopted based on the detection results. Results Mutations observed in MPE cell blocks included epidermal growth factor receptor mutation (EGFR) (60.4% [61/101]), anaplastic lymphoma kinase fusion (6.3% [5/80]), and ROS proto‐oncogene 1 receptor tyrosine kinase fusion (3% [2/70]). Other mutations that were found in <5% of patients included epidermal growth factor receptor‐2, rat sarcoma‐filtered germ carcinogenic homologous B1, neuroblastoma RAS viral oncogene homolog, and mesenchymal epithelial transition factor exon 14. The median follow‐up time was 23.5 months for the 41 patients with a single EGFR mutation and who received tyrosine kinase inhibitor monotherapy as the first‐line treatment; in these patients, the objective response rate was 78% (95% confidence intervals (CI), 62% to 89%), progression‐free survival was 10.8 months (95% CI, 8.7 to 13.0 months), and overall survival was 31.7 months (95% CI, 13.9 to 49.4 months). Conclusions Malignant pleural effusion cell blocks are recommended for mutation testing for targeted therapies in patients with NSCLC.

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“…Molecularly targeted therapies that have been developed for a subgroup of non-small cell lung cancer (NSCLC) with endothelial growth factor receptor (EGFR) activating mutations firmly underlined the importance of an improved classification of lung cancer into specific subtypes that qualify for specialized therapeutic strategies. Tyrosine kinase inhibitors (TKIs) have demonstrated enhanced efficacy and reduced toxicity in EGFR-sensitive patients compared to classical chemotherapy treatments because of their ability to target specific molecular abnormalities associated with NSCLC cells [8][9][10][11][12][13].…”

Section: Introductionmentioning

confidence: 99%

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

Gorachinov¹,

Mraiche²,

Moustafa³

et al. 2023

Beilstein J. Nanotechnol.

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Genomic and proteomic mutation analysis is the standard of care for selecting candidates for therapies with tyrosine kinase inhibitors against the human epidermal growth factor receptor (EGFR TKI therapies) and further monitoring cancer treatment efficacy and cancer development. Acquired resistance due to various genetic aberrations is an unavoidable problem during EGFR TKI therapy, leading to the rapid exhaustion of standard molecularly targeted therapeutic options against mutant variants. Attacking multiple molecular targets within one or several signaling pathways by co-delivery of multiple agents is a viable strategy for overcoming and preventing resistance to EGFR TKIs. However, because of the difference in pharmacokinetics among agents, combined therapies may not effectively reach their targets. The obstacles regarding the simultaneous co-delivery of therapeutic agents at the site of action can be overcome using nanomedicine as a platform and nanotools as delivery agents. Precision oncology research to identify targetable biomarkers and optimize tumor homing agents, hand in hand with designing multifunctional and multistage nanocarriers that respond to the inherent heterogeneity of the tumors, may resolve the challenges of inadequate tumor localization, improve intracellular internalization, and bring advantages over conventional nanocarriers.

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Detecting EGFR mutations and ALK/ROS1 rearrangements in non‐small cell lung cancer using malignant pleural effusion samples

Cited by 10 publications

References 24 publications

Multigene Combined Detection by RT-qPCR Using Cytological Specimens

Multigene Combined Detection by RT-qPCR Using Cytological Specimens

Role of molecular testing for malignant pleural effusion in targeted therapy for advanced non‐small cell lung cancer

Nanotechnology – a robust tool for fighting the challenges of drug resistance in non-small cell lung cancer

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