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A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients
Introduction The aim of this study was to examine whether a combined test using both cell sediment and supernatant cytology cell‐free DNA (ccfDNA) is more useful in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA alone in pleural effusion of lung cancer patients. Methods A...
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| Published in: | Cytopathology (Oxford) 2018-04, Vol.29 (2), p.150-155 |
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| container_title | Cytopathology (Oxford) |
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| creator | Kawahara, A. Fukumitsu, C. Azuma, K. Taira, T. Abe, H. Takase, Y. Murata, K. Sadashima, E. Hattori, S. Naito, Y. Akiba, J. |
| description | Introduction
The aim of this study was to examine whether a combined test using both cell sediment and supernatant cytology cell‐free DNA (ccfDNA) is more useful in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA alone in pleural effusion of lung cancer patients.
Methods
A total of 74 lung adenocarcinoma patients with paired samples between primary tumour and corresponding metastatic tumour with both cell sediment and supernatant ccfDNA of pleural effusion cytology were enrolled in this study. Cell sediment and supernatant ccfDNA were analysed separately for EGFR mutations by polymerase chain reaction.
Results
Out of 45 patients with mutant EGFR in primary tumours, EGFR mutations were detected in 23 cell sediments of corresponding metastases (sensitivity; 51.1%) and 20 supernatant ccfDNA corresponding metastases (sensitivity; 44.4%). By contrast, the combined test detected EGFR mutations in 27 corresponding metastases (sensitivity; 60.0%), and had a higher sensitivity than the cell sediment or the supernatant ccfDNA alone (P |
| doi_str_mv | 10.1111/cyt.12517 |
| format | article |
| fullrecord | <record><control><sourceid>proquest_cross</sourceid><recordid>TN_cdi_proquest_miscellaneous_1990855903</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1990855903</sourcerecordid><originalsourceid>FETCH-LOGICAL-c3887-c235dd50961f0ebddcd39cab71aa49b593c538e8b3692770c6dc86741b4a240c3</originalsourceid><addsrcrecordid>eNp1kU9u1TAQxi0Eoq-FBRdAltjAIq0dx0m8fHr9K1VUQmXBKnLsCXWVOMF2Wr0dR-A0PRAnYdJXWCDVm_HM_PSNPR8h7zg75HiOzDYd8lzy6gVZcVHKLBdMvCQrpmSZScmqPbIf4y1jPFe5eE32ciVKURd8RR7WdDMOrfNgaYKY6Byd_07bMd1QA31PI1g3gE9Ue0vjPEHwOmnMl-7vn7-6AECPP6-p83TqYQ66p9B1KDN6Gm_G-4gdE0CjEIr56JK7c2m78BYSmLTM0xju9OP15Oz0Cx3mhBkqINXPWDXaGwh0wio-Jr4hrzrdR3j7FA_I19OT6815dnl1drFZX2ZG1HWVmVxIayVTJe8YtNYaK5TRbcW1LlQrlTBS1FC3olR5VTFTWlOXVcHbQucFM-KAfNzpTmH8MeN-msHF5efawzjHhivFaikVE4h--A-9HWdcVh-bnPEKB_CSI_VpR5kwxhiga6bgBh22DWfNYmaDZjaPZiL7_klxbgew_8i_7iFwtAPuXQ_b55WazbfrneQfRTes6g</addsrcrecordid><sourcetype>Aggregation Database</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2017692161</pqid></control><display><type>article</type><title>A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients</title><source>Wiley-Blackwell Read & Publish Collection</source><creator>Kawahara, A. ; Fukumitsu, C. ; Azuma, K. ; Taira, T. ; Abe, H. ; Takase, Y. ; Murata, K. ; Sadashima, E. ; Hattori, S. ; Naito, Y. ; Akiba, J.</creator><creatorcontrib>Kawahara, A. ; Fukumitsu, C. ; Azuma, K. ; Taira, T. ; Abe, H. ; Takase, Y. ; Murata, K. ; Sadashima, E. ; Hattori, S. ; Naito, Y. ; Akiba, J.</creatorcontrib><description>Introduction
The aim of this study was to examine whether a combined test using both cell sediment and supernatant cytology cell‐free DNA (ccfDNA) is more useful in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA alone in pleural effusion of lung cancer patients.
Methods
A total of 74 lung adenocarcinoma patients with paired samples between primary tumour and corresponding metastatic tumour with both cell sediment and supernatant ccfDNA of pleural effusion cytology were enrolled in this study. Cell sediment and supernatant ccfDNA were analysed separately for EGFR mutations by polymerase chain reaction.
Results
Out of 45 patients with mutant EGFR in primary tumours, EGFR mutations were detected in 23 cell sediments of corresponding metastases (sensitivity; 51.1%) and 20 supernatant ccfDNA corresponding metastases (sensitivity; 44.4%). By contrast, the combined test detected EGFR mutations in 27 corresponding metastases (sensitivity; 60.0%), and had a higher sensitivity than the cell sediment or the supernatant ccfDNA alone (P < .05). Out of 45 patients with mutant EGFR, 24, three and 18 were cytologically diagnosed as positive, atypical or negative, respectively. The detection rate in the combined test was highest (95.8%) in the positive group, and mutant EGFR was also detected in four of 18 samples (22.2%) in the negative group.
Conclusions
A combined test using both cell sediment DNA and supernatant ccfDNA samples increases the concordance rate of EGFR mutations between primary tumour and corresponding metastases. Our findings indicate that supernatant ccfDNA is useful even in cases where the cytological diagnosis is negative.
Most non‐small cell lung cancer patients with EGFR mutations benefit from treatment with EGFR‐TKIs. A combined test using both cell sediment DNA and supernatant cell free DNA samples increases the concordance rate of EGFR mutations between primary tumor and corresponding metastases. Supernatant DNA may compensate for a lack of adequate cellular DNA in EGFR mutation analysis, and can be used to detect EGFR mutation in the same way as in cancer cell sediments.</description><identifier>ISSN: 0956-5507</identifier><identifier>EISSN: 1365-2303</identifier><identifier>DOI: 10.1111/cyt.12517</identifier><identifier>PMID: 29363841</identifier><language>eng</language><publisher>England: Wiley Subscription Services, Inc</publisher><subject>Adenocarcinoma ; Aged ; Aged, 80 and over ; Cellular biology ; Circulating Tumor DNA - genetics ; Circulating Tumor DNA - isolation & purification ; combined test ; Cytology ; cytology supernatant cell‐free DNA ; Deoxyribonucleic acid ; DNA ; DNA Mutational Analysis - methods ; epidermal growth factor receptor mutation ; Epidermal growth factor receptors ; ErbB Receptors - genetics ; Female ; Humans ; Lung cancer ; Lung Neoplasms - diagnosis ; Lung Neoplasms - genetics ; Lung Neoplasms - metabolism ; Lung Neoplasms - pathology ; Male ; Metastases ; Metastasis ; Middle Aged ; Mutation ; Neoplasm Proteins - genetics ; Pleural effusion ; pleural effusion cytology ; Pleural Effusion, Malignant - diagnosis ; Pleural Effusion, Malignant - genetics ; Pleural Effusion, Malignant - metabolism ; Pleural Effusion, Malignant - pathology ; Polymerase chain reaction ; Polymerase Chain Reaction - methods ; Sediments ; Tumors</subject><ispartof>Cytopathology (Oxford), 2018-04, Vol.29 (2), p.150-155</ispartof><rights>2018 John Wiley & Sons Ltd</rights><rights>2018 John Wiley & Sons Ltd.</rights><rights>Copyright © 2018 John Wiley & Sons Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3887-c235dd50961f0ebddcd39cab71aa49b593c538e8b3692770c6dc86741b4a240c3</citedby><cites>FETCH-LOGICAL-c3887-c235dd50961f0ebddcd39cab71aa49b593c538e8b3692770c6dc86741b4a240c3</cites><orcidid>0000-0001-5292-2785 ; 0000-0002-4081-2519</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/29363841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Kawahara, A.</creatorcontrib><creatorcontrib>Fukumitsu, C.</creatorcontrib><creatorcontrib>Azuma, K.</creatorcontrib><creatorcontrib>Taira, T.</creatorcontrib><creatorcontrib>Abe, H.</creatorcontrib><creatorcontrib>Takase, Y.</creatorcontrib><creatorcontrib>Murata, K.</creatorcontrib><creatorcontrib>Sadashima, E.</creatorcontrib><creatorcontrib>Hattori, S.</creatorcontrib><creatorcontrib>Naito, Y.</creatorcontrib><creatorcontrib>Akiba, J.</creatorcontrib><title>A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients</title><title>Cytopathology (Oxford)</title><addtitle>Cytopathology</addtitle><description>Introduction
The aim of this study was to examine whether a combined test using both cell sediment and supernatant cytology cell‐free DNA (ccfDNA) is more useful in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA alone in pleural effusion of lung cancer patients.
Methods
A total of 74 lung adenocarcinoma patients with paired samples between primary tumour and corresponding metastatic tumour with both cell sediment and supernatant ccfDNA of pleural effusion cytology were enrolled in this study. Cell sediment and supernatant ccfDNA were analysed separately for EGFR mutations by polymerase chain reaction.
Results
Out of 45 patients with mutant EGFR in primary tumours, EGFR mutations were detected in 23 cell sediments of corresponding metastases (sensitivity; 51.1%) and 20 supernatant ccfDNA corresponding metastases (sensitivity; 44.4%). By contrast, the combined test detected EGFR mutations in 27 corresponding metastases (sensitivity; 60.0%), and had a higher sensitivity than the cell sediment or the supernatant ccfDNA alone (P < .05). Out of 45 patients with mutant EGFR, 24, three and 18 were cytologically diagnosed as positive, atypical or negative, respectively. The detection rate in the combined test was highest (95.8%) in the positive group, and mutant EGFR was also detected in four of 18 samples (22.2%) in the negative group.
Conclusions
A combined test using both cell sediment DNA and supernatant ccfDNA samples increases the concordance rate of EGFR mutations between primary tumour and corresponding metastases. Our findings indicate that supernatant ccfDNA is useful even in cases where the cytological diagnosis is negative.
Most non‐small cell lung cancer patients with EGFR mutations benefit from treatment with EGFR‐TKIs. A combined test using both cell sediment DNA and supernatant cell free DNA samples increases the concordance rate of EGFR mutations between primary tumor and corresponding metastases. Supernatant DNA may compensate for a lack of adequate cellular DNA in EGFR mutation analysis, and can be used to detect EGFR mutation in the same way as in cancer cell sediments.</description><subject>Adenocarcinoma</subject><subject>Aged</subject><subject>Aged, 80 and over</subject><subject>Cellular biology</subject><subject>Circulating Tumor DNA - genetics</subject><subject>Circulating Tumor DNA - isolation & purification</subject><subject>combined test</subject><subject>Cytology</subject><subject>cytology supernatant cell‐free DNA</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA Mutational Analysis - methods</subject><subject>epidermal growth factor receptor mutation</subject><subject>Epidermal growth factor receptors</subject><subject>ErbB Receptors - genetics</subject><subject>Female</subject><subject>Humans</subject><subject>Lung cancer</subject><subject>Lung Neoplasms - diagnosis</subject><subject>Lung Neoplasms - genetics</subject><subject>Lung Neoplasms - metabolism</subject><subject>Lung Neoplasms - pathology</subject><subject>Male</subject><subject>Metastases</subject><subject>Metastasis</subject><subject>Middle Aged</subject><subject>Mutation</subject><subject>Neoplasm Proteins - genetics</subject><subject>Pleural effusion</subject><subject>pleural effusion cytology</subject><subject>Pleural Effusion, Malignant - diagnosis</subject><subject>Pleural Effusion, Malignant - genetics</subject><subject>Pleural Effusion, Malignant - metabolism</subject><subject>Pleural Effusion, Malignant - pathology</subject><subject>Polymerase chain reaction</subject><subject>Polymerase Chain Reaction - methods</subject><subject>Sediments</subject><subject>Tumors</subject><issn>0956-5507</issn><issn>1365-2303</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kU9u1TAQxi0Eoq-FBRdAltjAIq0dx0m8fHr9K1VUQmXBKnLsCXWVOMF2Wr0dR-A0PRAnYdJXWCDVm_HM_PSNPR8h7zg75HiOzDYd8lzy6gVZcVHKLBdMvCQrpmSZScmqPbIf4y1jPFe5eE32ciVKURd8RR7WdDMOrfNgaYKY6Byd_07bMd1QA31PI1g3gE9Ue0vjPEHwOmnMl-7vn7-6AECPP6-p83TqYQ66p9B1KDN6Gm_G-4gdE0CjEIr56JK7c2m78BYSmLTM0xju9OP15Oz0Cx3mhBkqINXPWDXaGwh0wio-Jr4hrzrdR3j7FA_I19OT6815dnl1drFZX2ZG1HWVmVxIayVTJe8YtNYaK5TRbcW1LlQrlTBS1FC3olR5VTFTWlOXVcHbQucFM-KAfNzpTmH8MeN-msHF5efawzjHhivFaikVE4h--A-9HWdcVh-bnPEKB_CSI_VpR5kwxhiga6bgBh22DWfNYmaDZjaPZiL7_klxbgew_8i_7iFwtAPuXQ_b55WazbfrneQfRTes6g</recordid><startdate>201804</startdate><enddate>201804</enddate><creator>Kawahara, A.</creator><creator>Fukumitsu, C.</creator><creator>Azuma, K.</creator><creator>Taira, T.</creator><creator>Abe, H.</creator><creator>Takase, Y.</creator><creator>Murata, K.</creator><creator>Sadashima, E.</creator><creator>Hattori, S.</creator><creator>Naito, Y.</creator><creator>Akiba, J.</creator><general>Wiley Subscription Services, Inc</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QP</scope><scope>7TK</scope><scope>7X8</scope><orcidid>https://orcid.org/0000-0001-5292-2785</orcidid><orcidid>https://orcid.org/0000-0002-4081-2519</orcidid></search><sort><creationdate>201804</creationdate><title>A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients</title><author>Kawahara, A. ; Fukumitsu, C. ; Azuma, K. ; Taira, T. ; Abe, H. ; Takase, Y. ; Murata, K. ; Sadashima, E. ; Hattori, S. ; Naito, Y. ; Akiba, J.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3887-c235dd50961f0ebddcd39cab71aa49b593c538e8b3692770c6dc86741b4a240c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Adenocarcinoma</topic><topic>Aged</topic><topic>Aged, 80 and over</topic><topic>Cellular biology</topic><topic>Circulating Tumor DNA - genetics</topic><topic>Circulating Tumor DNA - isolation & purification</topic><topic>combined test</topic><topic>Cytology</topic><topic>cytology supernatant cell‐free DNA</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA Mutational Analysis - methods</topic><topic>epidermal growth factor receptor mutation</topic><topic>Epidermal growth factor receptors</topic><topic>ErbB Receptors - genetics</topic><topic>Female</topic><topic>Humans</topic><topic>Lung cancer</topic><topic>Lung Neoplasms - diagnosis</topic><topic>Lung Neoplasms - genetics</topic><topic>Lung Neoplasms - metabolism</topic><topic>Lung Neoplasms - pathology</topic><topic>Male</topic><topic>Metastases</topic><topic>Metastasis</topic><topic>Middle Aged</topic><topic>Mutation</topic><topic>Neoplasm Proteins - genetics</topic><topic>Pleural effusion</topic><topic>pleural effusion cytology</topic><topic>Pleural Effusion, Malignant - diagnosis</topic><topic>Pleural Effusion, Malignant - genetics</topic><topic>Pleural Effusion, Malignant - metabolism</topic><topic>Pleural Effusion, Malignant - pathology</topic><topic>Polymerase chain reaction</topic><topic>Polymerase Chain Reaction - methods</topic><topic>Sediments</topic><topic>Tumors</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Kawahara, A.</creatorcontrib><creatorcontrib>Fukumitsu, C.</creatorcontrib><creatorcontrib>Azuma, K.</creatorcontrib><creatorcontrib>Taira, T.</creatorcontrib><creatorcontrib>Abe, H.</creatorcontrib><creatorcontrib>Takase, Y.</creatorcontrib><creatorcontrib>Murata, K.</creatorcontrib><creatorcontrib>Sadashima, E.</creatorcontrib><creatorcontrib>Hattori, S.</creatorcontrib><creatorcontrib>Naito, Y.</creatorcontrib><creatorcontrib>Akiba, J.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Calcium & Calcified Tissue Abstracts</collection><collection>Neurosciences Abstracts</collection><collection>MEDLINE - Academic</collection><jtitle>Cytopathology (Oxford)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Kawahara, A.</au><au>Fukumitsu, C.</au><au>Azuma, K.</au><au>Taira, T.</au><au>Abe, H.</au><au>Takase, Y.</au><au>Murata, K.</au><au>Sadashima, E.</au><au>Hattori, S.</au><au>Naito, Y.</au><au>Akiba, J.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients</atitle><jtitle>Cytopathology (Oxford)</jtitle><addtitle>Cytopathology</addtitle><date>2018-04</date><risdate>2018</risdate><volume>29</volume><issue>2</issue><spage>150</spage><epage>155</epage><pages>150-155</pages><issn>0956-5507</issn><eissn>1365-2303</eissn><abstract>Introduction
The aim of this study was to examine whether a combined test using both cell sediment and supernatant cytology cell‐free DNA (ccfDNA) is more useful in detecting EGFR mutation than using cell sediment DNA or supernatant ccfDNA alone in pleural effusion of lung cancer patients.
Methods
A total of 74 lung adenocarcinoma patients with paired samples between primary tumour and corresponding metastatic tumour with both cell sediment and supernatant ccfDNA of pleural effusion cytology were enrolled in this study. Cell sediment and supernatant ccfDNA were analysed separately for EGFR mutations by polymerase chain reaction.
Results
Out of 45 patients with mutant EGFR in primary tumours, EGFR mutations were detected in 23 cell sediments of corresponding metastases (sensitivity; 51.1%) and 20 supernatant ccfDNA corresponding metastases (sensitivity; 44.4%). By contrast, the combined test detected EGFR mutations in 27 corresponding metastases (sensitivity; 60.0%), and had a higher sensitivity than the cell sediment or the supernatant ccfDNA alone (P < .05). Out of 45 patients with mutant EGFR, 24, three and 18 were cytologically diagnosed as positive, atypical or negative, respectively. The detection rate in the combined test was highest (95.8%) in the positive group, and mutant EGFR was also detected in four of 18 samples (22.2%) in the negative group.
Conclusions
A combined test using both cell sediment DNA and supernatant ccfDNA samples increases the concordance rate of EGFR mutations between primary tumour and corresponding metastases. Our findings indicate that supernatant ccfDNA is useful even in cases where the cytological diagnosis is negative.
Most non‐small cell lung cancer patients with EGFR mutations benefit from treatment with EGFR‐TKIs. A combined test using both cell sediment DNA and supernatant cell free DNA samples increases the concordance rate of EGFR mutations between primary tumor and corresponding metastases. Supernatant DNA may compensate for a lack of adequate cellular DNA in EGFR mutation analysis, and can be used to detect EGFR mutation in the same way as in cancer cell sediments.</abstract><cop>England</cop><pub>Wiley Subscription Services, Inc</pub><pmid>29363841</pmid><doi>10.1111/cyt.12517</doi><tpages>6</tpages><orcidid>https://orcid.org/0000-0001-5292-2785</orcidid><orcidid>https://orcid.org/0000-0002-4081-2519</orcidid><oa>free_for_read</oa></addata></record> |
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| source | Wiley-Blackwell Read & Publish Collection |
| subjects | Adenocarcinoma Aged Aged, 80 and over Cellular biology Circulating Tumor DNA - genetics Circulating Tumor DNA - isolation & purification combined test Cytology cytology supernatant cell‐free DNA Deoxyribonucleic acid DNA DNA Mutational Analysis - methods epidermal growth factor receptor mutation Epidermal growth factor receptors ErbB Receptors - genetics Female Humans Lung cancer Lung Neoplasms - diagnosis Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Male Metastases Metastasis Middle Aged Mutation Neoplasm Proteins - genetics Pleural effusion pleural effusion cytology Pleural Effusion, Malignant - diagnosis Pleural Effusion, Malignant - genetics Pleural Effusion, Malignant - metabolism Pleural Effusion, Malignant - pathology Polymerase chain reaction Polymerase Chain Reaction - methods Sediments Tumors |
| title | A Combined test using both cell sediment and supernatant cell‐free DNA in pleural effusion shows increased sensitivity in detecting activating EGFR mutation in lung cancer patients |
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