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Molecular Screening of Small Biopsy Samples Using Next-Generation Sequencing in Korean Patients with Advanced Non-small Cell Lung Cancer: Korean Lung Cancer Consortium (KLCC-13-01)
Bo Mi Ku, Mi Hwa Heo, Joo-Hang Kim, Byoung Chul Cho, Eun Kyung Cho, Young Joo Min, Ki Hyeong Lee, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park, Tae Jung Kim, Ho Yun Lee, Hojoong Kim, Kyung-Jong Lee, Myung-Ju Ahn
J Pathol Transl Med. 2018;52(3):148-156.   Published online March 26, 2018
DOI: https://doi.org/10.4132/jptm.2018.03.12
  • 7,811 View
  • 301 Download
  • 16 Web of Science
  • 13 Crossref
AbstractAbstract PDF
Background
Non-small cell lung cancer (NSCLC) is a common type of cancer with poor prognosis. As individual cancers exhibit unique mutation patterns, identifying and characterizing gene mutations in NSCLC might help predict patient outcomes and guide treatment. The aim of this study was to evaluate the clinical adequacy of molecular testing using next-generation sequencing (NGS) for small biopsy samples and characterize the mutational landscape of Korean patients with advanced NSCLC.
Methods
DNA was extracted from small biopsy samples of 162 patients with advanced NSCLC. Targeted NGS of genomic alterations was conducted using Ion AmpliSeq Cancer Hotspot Panel v2.
Results
The median age of patients was 64 years (range, 32 to 83 years) and the majority had stage IV NSCLC at the time of cancer diagnosis (90%). Among the 162 patients, 161 patients (99.4%) had novel or hotspot mutations (range, 1 to 21 mutated genes). Mutations were found in 41 genes. Three of the most frequently mutated genes were TP53 (151, 93.2%), KDR (104, 64.2%), and epidermal growth factor receptor (EGFR; 69, 42.6%). We also observed coexistence of EGFR and other oncogene (such as KRAS, PIC3CA, PTEN, and STK11) mutations. Given that 69.6% (48/69) of EGFR mutant patients were treated with EGFR tyrosine kinase inhibitors, EGFR mutant status had higher prognostic ability in this study.
Conclusions
These results suggest that targeted NGS using small biopsy samples is feasible and allows for the detection of both common and rare mutations in NSCLC.

Citations

Citations to this article as recorded by  
  • PTEN, PTENP1, microRNAs, and ceRNA Networks: Precision Targeting in Cancer Therapeutics
    Glena Travis, Eileen M. McGowan, Ann M. Simpson, Deborah J. Marsh, Najah T. Nassif
    Cancers.2023; 15(20): 4954.     CrossRef
  • Worldwide Prevalence of Epidermal Growth Factor Receptor Mutations in Non-Small Cell Lung Cancer: A Meta-Analysis
    Barbara Melosky, Kato Kambartel, Maik Häntschel, Margherita Bennetts, Dana J. Nickens, Julia Brinkmann, Antonin Kayser, Michael Moran, Federico Cappuzzo
    Molecular Diagnosis & Therapy.2022; 26(1): 7.     CrossRef
  • Landscape of EGFR mutations in lung adenocarcinoma: a single institute experience with comparison of PANAMutyper testing and targeted next-generation sequencing
    Jeonghyo Lee, Yeon Bi Han, Hyun Jung Kwon, Song Kook Lee, Hyojin Kim, Jin-Haeng Chung
    Journal of Pathology and Translational Medicine.2022; 56(5): 249.     CrossRef
  • Suitability of transbronchial brushing cytology specimens for next‐generation sequencing in peripheral lung cancer
    Naoki Furuya, Shingo Matsumoto, Kazutaka Kakinuma, Kei Morikawa, Takeo Inoue, Hisashi Saji, Koichi Goto, Masamichi Mineshita
    Cancer Science.2021; 112(1): 380.     CrossRef
  • KLHL38 involvement in non-small cell lung cancer progression via activation of the Akt signaling pathway
    Yitong Xu, Chenglong Wang, Xizi Jiang, Yao Zhang, Hongbo Su, Jun Jiang, Hongjiu Ren, Xueshan Qiu
    Cell Death & Disease.2021;[Epub]     CrossRef
  • Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
    Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
    Journal of Pathology and Translational Medicine.2021; 55(3): 181.     CrossRef
  • Targeting non-small cell lung cancer: driver mutation beyond epidermal growth factor mutation and anaplastic lymphoma kinase fusion
    Quincy S. Chu
    Therapeutic Advances in Medical Oncology.2020; 12: 175883591989575.     CrossRef
  • Concomitant Mutations in EGFR 19Del/L858R Mutation and Their Association with Response to EGFR-TKIs in NSCLC Patients


    Hengrui Liang, Caichen Li, Yi Zhao, Shen Zhao, Jun Huang, Xiuyu Cai, Bo Cheng, Shan Xiong, Jianfu Li, Wei Wang, Changbin Zhu, Weiwei Li, Jianxing He, Wenhua Liang
    Cancer Management and Research.2020; Volume 12: 8653.     CrossRef
  • Prognostic role of Rab27A and Rab27B expression in patients with non‐small cell lung carcinoma
    Hyun Min Koh, Dae Hyun Song
    Thoracic Cancer.2019; 10(2): 143.     CrossRef
  • PD‐L1 expression in ROS1‐rearranged non‐small cell lung cancer: A study using simultaneous genotypic screening of EGFR, ALK, and ROS1
    Jongmin Lee, Chan Kwon Park, Hyoung‐Kyu Yoon, Young Jo Sa, In Sook Woo, Hyo Rim Kim, Sue Youn Kim, Tae‐Jung Kim
    Thoracic Cancer.2019; 10(1): 103.     CrossRef
  • Targeted Next-Generation Sequencing Validates the Use of Diagnostic Biopsies as a Suitable Alternative to Resection Material for Mutation Screening in Colorectal Cancer
    Hersh A. Ham-Karim, Henry Okuchukwu Ebili, Kirsty Manger, Wakkas Fadhil, Narmeen S. Ahmad, Susan D. Richman, Mohammad Ilyas
    Molecular Diagnosis & Therapy.2019; 23(3): 383.     CrossRef
  • Small lung tumor biopsy samples are feasible for high quality targeted next generation sequencing
    Hidenori Kage, Shinji Kohsaka, Aya Shinozaki‐Ushiku, Yoshihisa Hiraishi, Jiro Sato, Kazuhiro Nagayama, Tetsuo Ushiku, Daiya Takai, Jun Nakajima, Kiyoshi Miyagawa, Hiroyuki Aburatani, Hiroyuki Mano, Takahide Nagase
    Cancer Science.2019; 110(8): 2652.     CrossRef
  • PTEN in Lung Cancer: Dealing with the Problem, Building on New Knowledge and Turning the Game Around
    Anastasios Gkountakos, Giulia Sartori, Italia Falcone, Geny Piro, Ludovica Ciuffreda, Carmine Carbone, Giampaolo Tortora, Aldo Scarpa, Emilio Bria, Michele Milella, Rafael Rosell, Vincenzo Corbo, Sara Pilotto
    Cancers.2019; 11(8): 1141.     CrossRef
Comparison of Cytologic Evaluation between Conventional Method and CellprepPlus(R) Liquid-Based Cytology in Body Fluid.
Ji Hae Koo, Ho Chang Lee, Hyung Geun Song, Hye Suk Han, Ki Hyeong Lee, Kang Hyeon Choe, Ki Man Lee, Ok Jun Lee
Korean J Pathol. 2009;43(5):448-452.
DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.448
  • 4,585 View
  • 110 Download
  • 5 Crossref
AbstractAbstract PDF
BACKGROUND
Assessment of body fluid cytology is a useful means of evaluating a metastatic tumor. Liquid-based cytology (LBC) has been developed as a replacement for the conventional Papanicolaou (CP) test. This study was performed to compare CellprepPlus(R) LBC with CP in cytologic diagnosis. METHODS: Body fluid samples (n=188, including 72 peritoneal fluid and 116 pleural fluid samples) were divided equally and analyzed by both CellprepPlus(R) and CP.
RESULTS
CellprepPlus(R) revealed distributed thin layers of non-overlapping cells. All CellprepPlus(R) preparations were adequate, while 18 (9.57%) CP preparations were inadequate. The respective diagnostic rates of CellprepPlus(R) and CP were 75.0% and 76.1% negative, 10.6% and 6.38% atypical, 5.85% and 2.66% suspicious, and 8.51% and 5.32% malignant. Of the 58 confirmed cases, the sensitivity of CellprepPlus(R) and CP was 94.4% and 73.3%, respectively, and the negative predictive value was 97.2% and 87.9%, respectively.
CONCLUSIONS
CellprepPlus(R) LBC has better sensitivity and negative predictive value, and produces higher quality slide preparations than than CP, making it suitable as in screening of body fluid as a cytologic diagnostic tool.

Citations

Citations to this article as recorded by  
  • A COMPARATIVE STUDY OF CYTOLOGIC EVALUATION BETWEEN CONVENTIONAL METHOD & LIQUID BASED CYTOLOGY IN PLEURAL, PERICARDIAL & PERITONEAL FLUIDS
    R. P. Siddiqui, Mohd. Jafar Memon, Shraddha Sahu
    INTERNATIONAL JOURNAL OF SCIENTIFIC RESEARCH.2020; : 1.     CrossRef
  • Comparison of liquid-based cytology (CellPrepPlus) and conventional smears in pancreaticobiliary disease
    Myeong Ho Yeon, Hee Seok Jeong, Hee Seung Lee, Jong Soon Jang, Seungho Lee, Soon Man Yoon, Hee Bok Chae, Seon Mee Park, Sei Jin Youn, Joung-Ho Han, Hye-Suk Han, Ho Chang Lee
    The Korean Journal of Internal Medicine.2018; 33(5): 883.     CrossRef
  • Comparison of diagnostic accuracy between CellprepPlus® and ThinPrep® liquid‐based preparations in effusion cytology
    Yong‐Moon Lee, Ji‐Yong Hwang, Seung‐Myoung Son, Song‐Yi Choi, Ho‐Chang Lee, Eun‐Joong Kim, Hye‐Suk Han, Jin young An, Joung‐Ho Han, Ok‐Jun Lee
    Diagnostic Cytopathology.2014; 42(5): 384.     CrossRef
  • Evaluation of Urine Cytology in Urothelial Carcinoma Patients: A Comparison of CellprepPlus® Liquid-Based Cytology and Conventional Smear
    Seung-Myoung Son, Ji Hae Koo, Song-Yi Choi, Ho-Chang Lee, Yong-Moon Lee, Hyung Geun Song, Hae-Kyung Hwang, Hye-Suk Han, Seok-Joong Yun, Wun-Jae Kim, Eun-Joong Kim, Ok-Jun Lee
    Korean Journal of Pathology.2012; 46(1): 68.     CrossRef
  • CellprepPlus® Liquid-based Smear in Sono-guided Thyroid Fine Needle Aspiration: A Comparison of Conventional Method and CellprepPlus® Liquid-based Cytology
    Ji Hae Koo, Seung Young Lee, Ho-chang Lee, Jin-Woo Park, Sung Soo Koong, Tae Keun Oh, Hyun Jeong Jeon, Eun-Joong Kim, Ok-Jun Lee
    The Korean Journal of Pathology.2011; 45(2): 182.     CrossRef
Selective Neuronal Damage Produced by beta-fluoroethylacetate Intoxication in Rat Brain.
Ki Hyeong Lee, Beom Seok Jeon, Duk Lyul Na, Seong Ho Park, Je G Chi
Korean J Pathol. 1995;29(3):277-285.
  • 1,478 View
  • 13 Download
AbstractAbstract PDF
Beta-fluoroethylacetate has been extensively used as the rodenticide in Korea. In some patients with acute poisoning, beta-fluoroethylacetate caused cerebellar dysfunction as a single and persistent neurologic sequela after a period of an acute neurological disorder which is characterized by mental deterioration, seizures, and respiratory failure. But there has been no report of pathological findings to explain neurological deficit. We tried to verify the histologic changes of the central nervous systems in beta-fluoroethylacetate poisoned rats. Silver staining(Gallyas) was used to evaluate the histology. In acute intoxication experiment with LD50(7mg/Kg), beta-fluoroethylacetate elicited acute onset of consciousness deterioration, generalized tonic-clonic seizures and large amplitude tremulous activity involving whole body with full recovery after 24 hours. There was no discernible pathologic change in CNS in acutely poisoned rats. However, when poisoned with sublethal dose(5mg/Kg) daily for five days, a moderate degree of nerve cell degeneration was found selectively in dentate nucleus, Purkinie cell layer, vestibulo-cochlear nucleus and striatum. This change was not seen in hippocampus, cerebral cortex or cerebellar cortex. These findings were well correlated with the previous reports of selective pathology in human 5-FU intoxication cases. Our preliminary results suggest that beta-fluoroethylacetate, a kind of cellular metabolism inhibitor may induce selective neuropathology mainly involving cerebellar output pathway in rats.

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