Journal of Pathology and Translational Medicine

Original Articles

Non-small Cell Lung Cancer with Concomitant EGFR, KRAS, and ALK Mutation: Clinicopathologic Features of 12 Cases: Taebum Lee, Boram Lee, Yoon-La Choi, Joungho Han, Myung-Ju Ahn, Sang-Won Um; J Pathol Transl Med. 2016;50(3):197-203. Published online April 18, 2016; DOI: https://doi.org/10.4132/jptm.2016.03.09

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Background
Although epidermal growth factor receptor (EGFR), v-Ki-ras2 Kirsten rat sarcoma viral oncogene (KRAS), and anaplastic lymphoma kinase (ALK) mutations in non-small cell lung cancer (NSCLC) were thought to be mutually exclusive, some tumors harbor concomitant mutations. Discovering a driver mutation on the basis of morphologic features and therapeutic responses with mutation analysis can be used to understand pathogenesis and predict resistance in targeted therapy.
Methods
In 6,637 patients with NSCLC, 12 patients who had concomitant mutations were selected and clinicopathologic features were reviewed. Clinical characteristics included sex, age, smoking history, previous treatment, and targeted therapy with response and disease-free survival. Histologic features included dominant patterns, nuclear and cytoplasmic features.
Results
All patients were diagnosed with adenocarcinoma and had an EGFR mutation. Six patients had concomitant KRAS mutations and the other six had ALK mutations. Five of six EGFR-KRAS mutation patients showed papillary and acinar histologic patterns with hobnail cells. Three of six received EGFR tyrosine kinase inhibitor (TKI) and showed partial response for 7–29 months. All six EGFR-ALK mutation patients showed solid or cribriform patterns and three had signet ring cells. Five of six EGFR-ALK mutation patients received EGFR TKI and/or ALK inhibitor and four showed partial response or stable disease, except for one patient who had acquired an EGFR mutation.
Conclusions
EGFR and ALK mutations play an important role as driver mutations in double mutated NSCLC, and morphologic analysis can be used to predict treatment response.

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Critical Reviews™ in Oncogenesis.2024; 29(2): 1. CrossRef
Artificial Intelligence for Cardiothoracic Imaging: Overview of Current and Emerging Applications
Bruno Hochhegger, Romulo Pasini, Alysson Roncally Carvalho, Rosana Rodrigues, Stephan Altmayer, Leonardo Kayat Bittencourt, Edson Marchiori, Reza Forghani
Seminars in Roentgenology.2023; 58(2): 184. CrossRef
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Diego F. Chamorro, Andrés F. Cardona, July Rodríguez, Alejandro Ruiz-Patiño, Oscar Arrieta, Darwin A. Moreno-Pérez, Leonardo Rojas, Zyanya Lucia Zatarain-Barrón, Dora V. Ardila, Lucia Viola, Gonzalo Recondo, Juan B. Blaquier, Claudio Martín, Luis Raez, Su
Targeted Oncology.2023; 18(3): 425. CrossRef
Histone deacetylase inhibitor belinostat regulates metabolic reprogramming in killing KRAS‐mutant human lung cancer cells
Rebecca M. Peter, Md. Shahid Sarwar, Sarah Z. Mostafa, Yujue Wang, Xiaoyang Su, Ah‐Ng Kong
Molecular Carcinogenesis.2023; 62(8): 1136. CrossRef
Differential Distribution of Brain Metastases from Non-Small Cell Lung Cancer Based on Mutation Status
Bihong T. Chen, Taihao Jin, Ningrong Ye, Sean W. Chen, Russell C. Rockne, Stephanie Yoon, Isa Mambetsariev, Ebenezer Daniel, Ravi Salgia
Brain Sciences.2023; 13(7): 1057. CrossRef
Clinicopathological features and prognostic significance of pulmonary adenocarcinoma with signet ring cell components: meta-analysis and SEER analysis
Yang Tan, Ying-he Huang, Jia-wen Xue, Rui Zhang, Run Liu, Yan Wang, Zhen-Bo Feng
Clinical and Experimental Medicine.2023; 23(8): 4341. CrossRef
Ganoderma microsporum immunomodulatory protein as an extracellular epidermal growth factor receptor (EGFR) degrader for suppressing EGFR-positive lung cancer cells
Wei-Jyun Hua, Hsin Yeh, Zhi-Hu Lin, Ai-Jung Tseng, Li-Chen Huang, Wei-Lun Qiu, Tsung-Hsi Tu, Ding-Han Wang, Wei-Hung Hsu, Wei-Lun Hwang, Tung-Yi Lin
Cancer Letters.2023; 578: 216458. CrossRef
Next generation sequencing for detection of EGFR alterations in NSCLC: is more better?
Ullas Batra, Shrinidhi Nathany, Mansi Sharma, Parveen Jain, Anurag Mehta
Journal of Clinical Pathology.2022; 75(3): 164. CrossRef
Enkurin domain containing 1 (ENKD1) regulates the proliferation, migration and invasion of non‐small cell lung cancer cells
Ting Song, Peng Zhou, Chunjiao Sun, Na He, Haixia Li, Jie Ran, Jun Zhou, Yue Wu, Min Liu
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Targeting Mutant Kirsten Rat Sarcoma Viral Oncogene Homolog in Non-Small Cell Lung Cancer: Current Difficulties, Integrative Treatments and Future Perspectives
Jia-Xin Li, Run-Ze Li, Lin-Rui Ma, Peng Wang, Dong-Han Xu, Jie Huang, Li-Qi Li, Ling Tang, Ying Xie, Elaine Lai-Han Leung, Pei-Yu Yan
Frontiers in Pharmacology.2022;[Epub] CrossRef
Histone H3K9 methyltransferase SETDB1 augments invadopodia formation to promote tumor metastasis
Shuhei Ueshima, Jia Fang
Oncogene.2022; 41(24): 3370. CrossRef
ESMO expert consensus statements on the management of EGFR mutant non-small-cell lung cancer
A. Passaro, N. Leighl, F. Blackhall, S. Popat, K. Kerr, M.J. Ahn, M.E. Arcila, O. Arrieta, D. Planchard, F. de Marinis, A.M. Dingemans, R. Dziadziuszko, C. Faivre-Finn, J. Feldman, E. Felip, G. Curigliano, R. Herbst, P.A. Jänne, T. John, T. Mitsudomi, T.
Annals of Oncology.2022; 33(5): 466. CrossRef
Molecular Targets in Lung Cancer: Study of the Evolution of Biomarkers Associated with Treatment with Tyrosine Kinase Inhibitors—Has NF1 Tumor Suppressor a Key Role in Acquired Resistance?
Begoña O. Alen, Lara S. Estévez-Pérez, María Teresa Hermida-Romero, Ana Reguera-Arias, Rosario García-Campelo, Mercedes de la Torre-Bravos, Ángel Concha
Cancers.2022; 14(14): 3323. CrossRef
Analytical and clinical validation of a custom 15-gene next-generation sequencing panel for the evaluation of circulating tumor DNA mutations in patients with advanced non-small-cell lung cancer
Yock Ping Chow, Norziha Zainul Abidin, Ken Siong Kow, Lye Mun Tho, Chieh Lee Wong, Rama Krishna Kancha
PLOS ONE.2022; 17(10): e0276161. CrossRef
Potential Therapeutic Strategy for EGFR-Mutant Lung Cancer With Concomitant EML4-ALK Rearrangement—Combination of EGFR Tyrosine Kinase Inhibitors and ALK Inhibitors
Ming-Hung Huang, Jih-Hsiang Lee, Pei-Shan Hung, James Chih-Hsin Yang
JTO Clinical and Research Reports.2022; 3(11): 100405. CrossRef
Artificial Intelligence in Lung Cancer Imaging: Unfolding the Future
Michaela Cellina, Maurizio Cè, Giovanni Irmici, Velio Ascenti, Natallia Khenkina, Marco Toto-Brocchi, Carlo Martinenghi, Sergio Papa, Gianpaolo Carrafiello
Diagnostics.2022; 12(11): 2644. CrossRef
A single center analysis of first-line treatment in advanced KRAS mutant non-small cell lung cancer: real-world practice
Yanxia Liu, Yuan Gao, Ying Wang, Cong Zhao, Zhiyun Zhang, Baolan Li, Tongmei Zhang
BMC Cancer.2022;[Epub] CrossRef
High frequency of KRAS and EGFR mutation profiles in BRAF-negative thyroid carcinomas in Indonesia
Didik Setyo Heriyanto, Vincent Laiman, Nikko Vanda Limantara, Widyan Putra Anantawikrama, Fara Silvia Yuliani, Rita Cempaka, Sumadi Lukman Anwar
BMC Research Notes.2022;[Epub] CrossRef
Targeted next-generation sequencing for cancer-associated gene mutation and copy number detection in 206 patients with non–small-cell lung cancer
Songbai Zheng, Xiaodan Wang, Ying Fu, Beibei Li, Jianhua Xu, Haifang Wang, Zhen Huang, Hui Xu, Yurong Qiu, Yaozhou Shi, Kui Li
Bioengineered.2021; 12(1): 791. CrossRef
How mathematical modeling could contribute to the quantification of metastatic tumor burden under therapy: insights in immunotherapeutic treatment of non-small cell lung cancer
Pirmin Schlicke, Christina Kuttler, Christian Schumann
Theoretical Biology and Medical Modelling.2021;[Epub] CrossRef
A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma
Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon
Journal of Pathology and Translational Medicine.2021; 55(2): 139. CrossRef
Malfeasance of KRAS mutations in carcinogenesis
Rupal Tripathi, Shrinidhi Nathany, Anurag Mehta, Ullas Batra, Sakshi Mattoo, Mansi Sharma
Clinical and Experimental Medicine.2021; 21(3): 439. CrossRef
Detection of Low-Frequency KRAS Mutations in cfDNA From EGFR-Mutated NSCLC Patients After First-Line EGFR Tyrosine Kinase Inhibitors
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Frontiers in Oncology.2021;[Epub] CrossRef
Non-Small Cell Lung Cancer Harboring Concurrent EGFR Genomic Alterations: A Systematic Review and Critical Appraisal of the Double Dilemma
Valerio Gristina, Maria La Mantia, Antonio Galvano, Sofia Cutaia, Nadia Barraco, Marta Castiglia, Alessandro Perez, Marco Bono, Federica Iacono, Martina Greco, Katia Calcara, Valentina Calò, Sergio Rizzo, Lorena Incorvaia, Maria Chiara Lisanti, Giulia San
Journal of Molecular Pathology.2021; 2(2): 173. CrossRef
Testing for EGFR Mutations and ALK Rearrangements in Advanced Non-Small-Cell Lung Cancer: Considerations for Countries in Emerging Markets
Mercedes L Dalurzo, Alejandro Avilés-Salas, Fernando Augusto Soares, Yingyong Hou, Yuan Li, Anna Stroganova, Büge Öz, Arif Abdillah, Hui Wan, Yoon-La Choi
OncoTargets and Therapy.2021; Volume 14: 4671. CrossRef
Untangling the KRAS mutated lung cancer subsets and its therapeutic implications
Kulshrestha Ritu, Pawan Kumar, Amit Singh, K. Nupur, Sonam Spalgias, Parul Mrigpuri, Rajkumar
Molecular Biomedicine.2021;[Epub] CrossRef
Lorlatinib Induces Durable Disease Stabilization in a Pancreatic Cancer Patient with a ROS1 p.L1950F Mutation: Case Report
Janna-Lisa Velthaus, Peter Iglauer, Ronald Simon, Carsten Bokemeyer, Peter Bannas, Niklas Beumer, Charles D. Imbusch, Eray Goekkurt, Sonja Loges
Oncology Research and Treatment.2021; 44(9): 495. CrossRef
Proteasome-dependent degradation of Smad7 is critical for lung cancer metastasis
Lu Tong, Shihui Shen, Quan Huang, Junjiang Fu, Tianzhen Wang, Linian Pan, Pei Zhang, Geng Chen, Tingmei Huang, Ke Li, Qingwu Liu, Shaofang Xie, Xiao Yang, Robb E. Moses, Xiaotao Li, Lei Li
Cell Death & Differentiation.2020; 27(6): 1795. CrossRef
Circulating cell-free DNA as a diagnostic and prognostic biomarker for non-small-cell lung cancer: a systematic review and meta-analysis
Zhoumiao Chen, Huiwen Miao, Qingxin Zeng, Shaohua Xu, Zhao Chen, Kai Liu
Biomarkers in Medicine.2020; 14(7): 587. CrossRef
Influence of EGFR-activating mutations on sensitivity to tyrosine kinase inhibitors in a KRAS mutant non-small cell lung cancer cell line
Yoshinori Tsukumo, Mikihiko Naito, Takayoshi Suzuki, Srikumar Chellappan
PLOS ONE.2020; 15(3): e0229712. CrossRef
KRAS oncogene may be another target conquered in non‐small cell lung cancer (NSCLC)
Hanxiao Chen, Jun Zhao
Thoracic Cancer.2020; 11(12): 3425. CrossRef
Epidemiologic Features of NSCLC Gene Alterations in Hispanic Patients from Puerto Rico
Ruifang Zheng, Zhiwei Yin, Albert Alhatem, Derek Lyle, Bei You, Andrew S. Jiang, Dongfang Liu, Zsolt Jobbagy, Qing Wang, Seena Aisner, Jie-Gen Jiang
Cancers.2020; 12(12): 3492. CrossRef
Comprehensive pancancer genomic analysis reveals (RTK)-RAS-RAF-MEK as a key dysregulated pathway in cancer: Its clinical implications
Robin Imperial, Omer M Toor, Arif Hussain, Janakiraman Subramanian, Ashiq Masood
Seminars in Cancer Biology.2019; 54: 14. CrossRef
Epidermal growth factor receptor (EGFR), KRAS, and BRAF mutations in lung adenocarcinomas: A study from India
Varsha Singh, Prerna Guleria, Prabhat Singh Malik, Anant Mohan, Sanjay Thulkar, R M Pandey, Kalpana Luthra, Sudheer Arava, Ruma Ray, Deepali Jain
Current Problems in Cancer.2019; 43(5): 391. CrossRef
Clinical Validation of Coexisting Activating Mutations Within EGFR, Mitogen-Activated Protein Kinase, and Phosphatidylinositol 3-Kinase Pathways in Lung Cancers
Federico De Marchi, Lisa Haley, Henderson Fryer, Junaid Ibrahim, Katie Beierl, Gang Zheng, Christopher D. Gocke, James R. Eshleman, Deborah Belchis, Peter Illei, Ming-Tseh Lin
Archives of Pathology & Laboratory Medicine.2019; 143(2): 174. CrossRef
A sequential Monte Carlo algorithm for inference of subclonal structure in cancer
Oyetunji E. Ogundijo, Kaiyi Zhu, Xiaodong Wang, Dimitris Anastassiou, Xiang Li
PLOS ONE.2019; 14(1): e0211213. CrossRef
The Presence of Concomitant Mutations Affects the Activity of EGFR Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer (NSCLC) Patients
Anna Rachiglio, Francesca Fenizia, Maria Piccirillo, Domenico Galetta, Lucio Crinò, Bruno Vincenzi, Emiddio Barletta, Carmine Pinto, Francesco Ferraù, Matilde Lambiase, Agnese Montanino, Cristin Roma, Vienna Ludovini, Elisabetta Montagna, Antonella De Luc
Cancers.2019; 11(3): 341. CrossRef
Concurrent Driver Gene Mutations as Negative Predictive Factors in Epidermal Growth Factor Receptor-Positive Non-Small Cell Lung Cancer
Minjiang Chen, Yan Xu, Jing Zhao, Wei Zhong, Li Zhang, Yalan Bi, Mengzhao Wang
EBioMedicine.2019; 42: 304. CrossRef
Anaplastic Lymphoma Kinase (ALK)-positive Tumors
Rohan Gupta, Idoroenyi Amanam, Syed Rahmanuddin, Isa Mambetsariev, Yingyu Wang, Charity Huang, Karen Reckamp, Lalit Vora, Ravi Salgia
American Journal of Clinical Oncology.2019; 42(4): 337. CrossRef
Clinical features and therapeutic options in non‐small cell lung cancer patients with concomitant mutations of EGFR, ALK, ROS1, KRAS or BRAF
Xibin Zhuang, Chao Zhao, Jiayu Li, Chunxia Su, Xiaoxia Chen, Shengxiang Ren, Xuefei Li, Caicun Zhou
Cancer Medicine.2019; 8(6): 2858. CrossRef
Intrinsic resistance to EGFR-Tyrosine Kinase Inhibitors in EGFR-Mutant Non-Small Cell Lung Cancer: Differences and Similarities with Acquired Resistance
Santoni-Rugiu, Melchior, Urbanska, Jakobsen, Stricker, Grauslund, Sørensen
Cancers.2019; 11(7): 923. CrossRef
Clinical outcome of treatment of metastatic non-small cell lung cancer in patients harboring uncommon EGFR mutation
J. Chantharasamee, N. Poungvarin, P. Danchaivijitr, S. Techawatanawanna
BMC Cancer.2019;[Epub] CrossRef
Deregulated lncRNA expression profile in the mouse lung adenocarcinomas with KRAS‐G12D mutation and P53 knockout
Meiqin Zhang, Nan Jiang, Renjie Cui, Sichen Du, Huayuan Ou, Tinglan Chen, Runsheng Ge, Duan Ma, Jin Zhang
Journal of Cellular and Molecular Medicine.2019; 23(10): 6978. CrossRef
Open-Sourced CIViC Annotation Pipeline to Identify and Annotate Clinically Relevant Variants Using Single-Molecule Molecular Inversion Probes
Erica K. Barnell, Adam Waalkes, Matt C. Mosior, Kelsi Penewit, Kelsy C. Cotto, Arpad M. Danos, Lana M. Sheta, Katie M. Campbell, Kilannin Krysiak, Damian Rieke, Nicholas C. Spies, Zachary L. Skidmore, Colin C. Pritchard, Todd A. Fehniger, Ravindra Uppalur
JCO Clinical Cancer Informatics.2019; (3): 1. CrossRef
EGFR, KRAS, BRAF, ALK, and cMET genetic alterations in 1440 Sardinian patients with lung adenocarcinoma
Maria Colombino, Panagiotis Paliogiannis, Antonio Cossu, Davide Adriano Santeufemia, Maria Cristina Sini, Milena Casula, Grazia Palomba, Antonella Manca, Marina Pisano, Valentina Doneddu, Giuseppe Palmieri
BMC Pulmonary Medicine.2019;[Epub] CrossRef
Concomitant Presence of EGFR and ALK Fusion Gene Mutation in Adenocarcinoma of Lung: A Case Report and Review of the Literature
Nishitha Thumallapally, Hana Yu, Mohammad Farhan, Uroosa Ibrahim, Maricel Odiami
Journal of Pharmacy Practice.2018; 31(2): 244. CrossRef
Double Trouble: A Case Series on Concomitant Genetic Aberrations in NSCLC
Nele Van Der Steen, Yves Mentens, Marc Ramael, Leticia G. Leon, Paul Germonpré, Jose Ferri, David R. Gandara, Elisa Giovannetti, Godefridus J. Peters, Patrick Pauwels, Christian Rolfo
Clinical Lung Cancer.2018; 19(1): 35. CrossRef
KRAS oncogene in non-small cell lung cancer: clinical perspectives on the treatment of an old target
Marta Román, Iosune Baraibar, Inés López, Ernest Nadal, Christian Rolfo, Silvestre Vicent, Ignacio Gil-Bazo
Molecular Cancer.2018;[Epub] CrossRef
Pulmonary Adenocarcinoma, Harboring Both an EGFR Mutation and ALK Rearrangement, Presenting a Stable Disease to Erlotinib and a Partial Response to Alectinib
Akira Yokoyama, Atsuhisa Tamura, Kazuko Miyakawa, Kei Kusaka, Masahiro Shimada, Takashi Hirose, Hirotoshi Matsui, Masashi Kitani, Akira Hebisawa, Ken Ohta
Internal Medicine.2018; 57(16): 2377. CrossRef
Long-term survival with erlotinib in advanced lung adenocarcinoma harboring synchronous EGFR G719S and KRAS G12C mutations
Biagio Ricciuti, Sara Baglivo, Vienna Ludovini, Angelo Sidoni, Giulio Metro, Marta Brambilla, Annamaria Siggillino, Maria Sole Reda, Alberto Rebonato, Daniele Maiettini, Rita Chiari
Lung Cancer.2018; 120: 70. CrossRef
Concomitant driver mutations in advanced EGFR-mutated non-small-cell lung cancer and their impact on erlotinib treatment
Jan Nyrop Jakobsen, Eric Santoni-Rugiu, Morten Grauslund, Linea Melchior, Jens Benn Sørensen
Oncotarget.2018; 9(40): 26195. CrossRef
Implications of KRAS mutations in acquired resistance to treatment in NSCLC
Marzia Del Re, Eleonora Rofi, Giuliana Restante, Stefania Crucitta, Elena Arrigoni, Stefano Fogli, Massimo Di Maio, Iacopo Petrini, Romano Danesi
Oncotarget.2018; 9(5): 6630. CrossRef
Alk Immunohistochemistry is Highly Sensitive and Specific for the Detection of Alk Translocated Lung Adenocarcinomas: Lessons from An Audit of Lung Cancer Molecular Testing
YC Kheng, K Walsh, L Williams, WA Wallace, DJ Harrison, A Oniscu
Journal of the Royal College of Physicians of Edinburgh.2018; 48(1): 20. CrossRef
Targeting KRAS mutated non-small cell lung cancer: A history of failures and a future of hope for a diverse entity
Alexios Matikas, Dimitrios Mistriotis, Vasilios Georgoulias, Athanasios Kotsakis
Critical Reviews in Oncology/Hematology.2017; 110: 1. CrossRef
Clinical Outcome of ALK -Positive Non–Small Cell Lung Cancer (NSCLC) Patients with De Novo EGFR or KRAS Co-Mutations Receiving Tyrosine Kinase Inhibitors (TKIs)
Sabine Schmid, Oliver Gautschi, Sacha Rothschild, Michael Mark, Patrizia Froesch, Dirk Klingbiel, Hermann Reichegger, Wolfram Jochum, Joachim Diebold, Martin Früh
Journal of Thoracic Oncology.2017; 12(4): 681. CrossRef
EGFR and KRAS molecular genotyping for pulmonary carcinomas: Feasibility of a simple and rapid technique implementable in any department of pathology
Vincent Thomas De Montpréville, Maria-Rosa Ghigna, Ludovic Lacroix, Antoinette Lemoine, Benjamin Besse, Olaf Mercier, Élie Fadel, Peter Dorfmuller, Thierry Le Chevalier
Pathology - Research and Practice.2017; 213(7): 793. CrossRef
MET Exon 14 Skipping Mutations in Lung Adenocarcinoma: Clinicopathologic Implications and Prognostic Values
Geun Dong Lee, Seung Eun Lee, Doo-Yi Oh, Dan-bi Yu, Hae Min Jeong, Jooseok Kim, Sungyoul Hong, Hun Soon Jung, Ensel Oh, Ji-Young Song, Mi-Sook Lee, Mingi Kim, Kyungsoo Jung, Jhingook Kim, Young Kee Shin, Yoon-La Choi, Hyeong Ryul Kim
Journal of Thoracic Oncology.2017; 12(8): 1233. CrossRef
Non-Small-Cell Lung Cancer (NSCLC) Harboring ALK Translocations: Clinical Characteristics and Management in a Real-Life Setting: a French Retrospective Analysis (GFPC 02–14 Study)
Jean-Bernard Auliac, Isabelle Monnet, Catherine Dubos-Arvis, Anne Marie Chiappa, Nathalie Baize, Suzana Bota, Alain Vergnenegre, Helene Doubre, Chrystele Locher, Acya Bizieux, Gilles Robinet, Christos Chouaid
Targeted Oncology.2017; 12(6): 833. CrossRef
Concomitant EML4-ALK rearrangement and EGFR mutation in non-small cell lung cancer patients: a literature review of 100 cases
Giuseppe Lo Russo, Martina Imbimbo, Giulia Corrao, Claudia Proto, Diego Signorelli, Milena Vitali, Monica Ganzinelli, Laura Botta, Nicoletta Zilembo, Filippo de Braud, Marina Chiara Garassino
Oncotarget.2017; 8(35): 59889. CrossRef
Management of non-small cell lung cancer in the era of personalized medicine
Gaetano Rocco, Alessandro Morabito, Alessandra Leone, Paolo Muto, Francesco Fiore, Alfredo Budillon
The International Journal of Biochemistry & Cell Biology.2016; 78: 173. CrossRef
A long-term survivor of non-small-cell lung cancer harboring concomitant EGFR mutation and ALK translocation
Fumio Imamura, Takako Inoue, Madoka Kimura, Kazumi Nishino, Toru Kumagai
Respiratory Medicine Case Reports.2016; 19: 137. CrossRef

PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors: Yooju Shin, Jiyeon Hyeon, Boram Lee, Sang Yun Ha, Min Eui Hong, In Gu Do, Kyoung-Mee Kim; J Pathol Transl Med. 2015;49(1):23-29. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.08

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Background
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

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Gaoxiu Qi, Jinmeng Liu, Shuqi Tao, Wenyuan Fan, Haoning Zheng, Meihong Wang, Hanchao Yang, Yongting Liu, Huancai Liu, Fenghua Zhou
PeerJ.2023; 11: e15675. CrossRef
Loss of Slfn3 induces a sex-dependent repair vulnerability after 50% bowel resection
Emilie E. Vomhof-DeKrey, Jack T. Lansing, Diane C. Darland, Josey Umthun, Allie D. Stover, Christopher Brown, Marc D. Basson
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(2): G136. CrossRef
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Napaporn Puripat, Kongsak Loharamtaweethong
Virchows Archiv.2019; 474(1): 87. CrossRef
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Cao Jin, Yan Huang, Mansoor Nasim, Yihe Yang, Lili Lee
International Journal of Surgical Pathology.2019; 27(7): 706. CrossRef
The utility of phosphohistone H3 in early prediction of benign and borderline phyllodes tumor recurrence
AymenM El-Saka, MohamedA Mlees, YomnaA Zamzam
Egyptian Journal of Pathology.2019; 39(2): 402. CrossRef
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BioMed Research International.2018; 2018: 1. CrossRef
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Scanning.2018; 2018: 1. CrossRef
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Histopathology.2017; 70(5): 746. CrossRef

Brief Case Report

An Unusual Case of Pulmonary Mucous Gland Adenoma with Fibromyxoid Stroma and Cartilage Islands in 68-Year-Old Woman: Boram Lee, In Ho Choi, Joungho Han, Kyung Soo Lee, Young Mog Shim; Korean J Pathol. 2014;48(2):167-169. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.167

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Annales de Pathologie.2021; 41(2): 192. CrossRef
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Original Article

KRAS Mutation Detection in Non-small Cell Lung Cancer Using a Peptide Nucleic Acid-Mediated Polymerase Chain Reaction Clamping Method and Comparative Validation with Next-Generation Sequencing: Boram Lee, Boin Lee, Gangmin Han, Mi Jung Kwon, Joungho Han, Yoon-La Choi; Korean J Pathol. 2014;48(2):100-107. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.100

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Abstract PDF

Background

KRAS is one of commonly mutated genetic "drivers" in non-small cell lung cancers (NSCLCs). Recent studies indicate that patients with KRAS-mutated tumors do not benefit from adjuvant chemotherapy, so there is now a focus on targeting KRAS-mutated NSCLCs. A feasible mutation detection method is required in order to accurately test for KRAS status.

Methods

We compared direct Sanger sequencing and the peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method in 134 NSCLCs and explored associations with clinicopathological factors. Next-generation sequencing (NGS) was used to validate the results of discordant cases. To increase the resolution of low-level somatic mutant molecules, PNA-mediated PCR clamping was used for mutant enrichment prior to NGS.

Results

Twenty-one (15.7%) cases were found to have the KRAS mutations using direct sequencing, with two additional cases by the PNA-mediated PCR clamping method. The frequencies of KRAS mutant alleles were 2% and 4%, respectively, using conventional NGS, increasing up to 90% and 89%, using mutant-enriched NGS. The KRAS mutation occurs more frequently in the tumors of smokers (p=.012) and in stage IV tumors (p=.032).

Conclusions

Direct sequencing can accurately detect mutations, but, it is not always possible to obtain a tumor sample with sufficient volume. The PNA-mediated PCR clamping can rapidly provide results with sufficient sensitivity.

Citations

Citations to this article as recorded by

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