Evaluation and diagnostic value of next‐generation sequencing analysis of residual liquid‐based cytology specimens of pancreatic masses
Background Liquid‐based cytology (LBC) is a widely used method for processing specimens obtained by endoscopic biopsy. This study evaluated next‐generation sequencing (NGS) analysis of LBC specimens to improve the diagnostic accuracy of pancreatic lesions. Methods Upon the diagnosis of a suspected p...
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Veröffentlicht in: | Cancer cytopathology 2022-03, Vol.130 (3), p.202-214 |
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creator | Sekita‐Hatakeyama, Yoko Fujii, Tomomi Nishikawa, Takeshi Mitoro, Akira Sawai, Masayoshi Itami, Hiroe Morita, Kouhei Uchiyama, Tomoko Takeda, Maiko Sho, Masayuki Yoshiji, Hitoshi Hatakeyama, Kinta Ohbayashi, Chiho |
description | Background
Liquid‐based cytology (LBC) is a widely used method for processing specimens obtained by endoscopic biopsy. This study evaluated next‐generation sequencing (NGS) analysis of LBC specimens to improve the diagnostic accuracy of pancreatic lesions.
Methods
Upon the diagnosis of a suspected pancreatic mass, LBC residues were used retrospectively. The quantity and quality of DNA extracted from residual LBC samples were evaluated, and an NGS analysis targeting 6 genes (KRAS, GNAS, TP53, CDKN2A, SMAD4, and PIK3CA) was performed.
Results
The library was prepared from LBC specimens taken from 52 cases: 44 were successful, and 8 preparations failed. An analysis of DNA quantity and quality suggested that the success or failure of NGS implementation depended on both properties. The final diagnosis was achieved by a combination of the pathological analysis of the surgical excision or biopsy material with clinical information. Among the 33 cases of pancreatic ductal adenocarcinoma (PDAC), KRAS, TP53, CDKN2A, and SMAD4 mutations were identified in 31 (94%), 16 (48%), 3 (9%), and 2 (6%), respectively. Among the 11 benign cases, only a KRAS mutation was identified in 1 case. On the basis of NGS results, 18 of 33 PDACs (55%) were classified as highly dysplastic or more, and 10 of 11 benign lesions were evaluated as nonmalignant, which was consistent with the final diagnosis.
Conclusions
NGS analysis using LBC specimens from which DNA of appropriate quantity and quality has been extracted could contribute to improving the assessment of pancreatic tumor malignancies and the application of molecular‐targeted drugs.
This article presents the feasibility of using a next‐generation sequencing (NGS) assay for liquid‐based cytology (LBC) specimens with DNA of sufficient quantity and quality. The detection of cancer‐related mutations by NGS using LBC demonstrates its value for the evaluation of malignancy. |
doi_str_mv | 10.1002/cncy.22525 |
format | Article |
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Liquid‐based cytology (LBC) is a widely used method for processing specimens obtained by endoscopic biopsy. This study evaluated next‐generation sequencing (NGS) analysis of LBC specimens to improve the diagnostic accuracy of pancreatic lesions.
Methods
Upon the diagnosis of a suspected pancreatic mass, LBC residues were used retrospectively. The quantity and quality of DNA extracted from residual LBC samples were evaluated, and an NGS analysis targeting 6 genes (KRAS, GNAS, TP53, CDKN2A, SMAD4, and PIK3CA) was performed.
Results
The library was prepared from LBC specimens taken from 52 cases: 44 were successful, and 8 preparations failed. An analysis of DNA quantity and quality suggested that the success or failure of NGS implementation depended on both properties. The final diagnosis was achieved by a combination of the pathological analysis of the surgical excision or biopsy material with clinical information. Among the 33 cases of pancreatic ductal adenocarcinoma (PDAC), KRAS, TP53, CDKN2A, and SMAD4 mutations were identified in 31 (94%), 16 (48%), 3 (9%), and 2 (6%), respectively. Among the 11 benign cases, only a KRAS mutation was identified in 1 case. On the basis of NGS results, 18 of 33 PDACs (55%) were classified as highly dysplastic or more, and 10 of 11 benign lesions were evaluated as nonmalignant, which was consistent with the final diagnosis.
Conclusions
NGS analysis using LBC specimens from which DNA of appropriate quantity and quality has been extracted could contribute to improving the assessment of pancreatic tumor malignancies and the application of molecular‐targeted drugs.
This article presents the feasibility of using a next‐generation sequencing (NGS) assay for liquid‐based cytology (LBC) specimens with DNA of sufficient quantity and quality. The detection of cancer‐related mutations by NGS using LBC demonstrates its value for the evaluation of malignancy.</description><identifier>ISSN: 1934-662X</identifier><identifier>EISSN: 1934-6638</identifier><identifier>DOI: 10.1002/cncy.22525</identifier><identifier>PMID: 34665935</identifier><language>eng</language><publisher>United States: Wiley Subscription Services, Inc</publisher><subject>Biopsy ; Carcinoma, Pancreatic Ductal - diagnosis ; Carcinoma, Pancreatic Ductal - genetics ; Carcinoma, Pancreatic Ductal - surgery ; Cellular biology ; Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods ; High-Throughput Nucleotide Sequencing - methods ; Humans ; liquid‐based cytology ; Mutation ; next‐generation sequencing ; Original ; Pancreatic cancer ; pancreatic ductal carcinoma ; pancreatic lesions ; Pancreatic Neoplasms ; Pancreatic Neoplasms - diagnosis ; Pancreatic Neoplasms - genetics ; Pancreatic Neoplasms - pathology ; Proto-Oncogene Proteins p21(ras) - genetics ; proto‐oncogene proteins p21(ras) ; Retrospective Studies</subject><ispartof>Cancer cytopathology, 2022-03, Vol.130 (3), p.202-214</ispartof><rights>2021 The Authors. published by Wiley Periodicals LLC on behalf of American Cancer Society.</rights><rights>2021 The Authors. Cancer Cytopathology published by Wiley Periodicals LLC on behalf of American Cancer Society.</rights><rights>2021. This article is published under http://creativecommons.org/licenses/by-nc-nd/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c5145-cb1c5817defcd007ab77939c1fd764b9d0dc7795f896b65acf69ef5a57b75aa63</citedby><cites>FETCH-LOGICAL-c5145-cb1c5817defcd007ab77939c1fd764b9d0dc7795f896b65acf69ef5a57b75aa63</cites><orcidid>0000-0001-7729-1836 ; 0000-0002-8046-9508</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1002%2Fcncy.22525$$EPDF$$P50$$Gwiley$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1002%2Fcncy.22525$$EHTML$$P50$$Gwiley$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,1417,1433,27924,27925,45574,45575,46409,46833</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/34665935$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sekita‐Hatakeyama, Yoko</creatorcontrib><creatorcontrib>Fujii, Tomomi</creatorcontrib><creatorcontrib>Nishikawa, Takeshi</creatorcontrib><creatorcontrib>Mitoro, Akira</creatorcontrib><creatorcontrib>Sawai, Masayoshi</creatorcontrib><creatorcontrib>Itami, Hiroe</creatorcontrib><creatorcontrib>Morita, Kouhei</creatorcontrib><creatorcontrib>Uchiyama, Tomoko</creatorcontrib><creatorcontrib>Takeda, Maiko</creatorcontrib><creatorcontrib>Sho, Masayuki</creatorcontrib><creatorcontrib>Yoshiji, Hitoshi</creatorcontrib><creatorcontrib>Hatakeyama, Kinta</creatorcontrib><creatorcontrib>Ohbayashi, Chiho</creatorcontrib><title>Evaluation and diagnostic value of next‐generation sequencing analysis of residual liquid‐based cytology specimens of pancreatic masses</title><title>Cancer cytopathology</title><addtitle>Cancer Cytopathol</addtitle><description>Background
Liquid‐based cytology (LBC) is a widely used method for processing specimens obtained by endoscopic biopsy. This study evaluated next‐generation sequencing (NGS) analysis of LBC specimens to improve the diagnostic accuracy of pancreatic lesions.
Methods
Upon the diagnosis of a suspected pancreatic mass, LBC residues were used retrospectively. The quantity and quality of DNA extracted from residual LBC samples were evaluated, and an NGS analysis targeting 6 genes (KRAS, GNAS, TP53, CDKN2A, SMAD4, and PIK3CA) was performed.
Results
The library was prepared from LBC specimens taken from 52 cases: 44 were successful, and 8 preparations failed. An analysis of DNA quantity and quality suggested that the success or failure of NGS implementation depended on both properties. The final diagnosis was achieved by a combination of the pathological analysis of the surgical excision or biopsy material with clinical information. Among the 33 cases of pancreatic ductal adenocarcinoma (PDAC), KRAS, TP53, CDKN2A, and SMAD4 mutations were identified in 31 (94%), 16 (48%), 3 (9%), and 2 (6%), respectively. Among the 11 benign cases, only a KRAS mutation was identified in 1 case. On the basis of NGS results, 18 of 33 PDACs (55%) were classified as highly dysplastic or more, and 10 of 11 benign lesions were evaluated as nonmalignant, which was consistent with the final diagnosis.
Conclusions
NGS analysis using LBC specimens from which DNA of appropriate quantity and quality has been extracted could contribute to improving the assessment of pancreatic tumor malignancies and the application of molecular‐targeted drugs.
This article presents the feasibility of using a next‐generation sequencing (NGS) assay for liquid‐based cytology (LBC) specimens with DNA of sufficient quantity and quality. The detection of cancer‐related mutations by NGS using LBC demonstrates its value for the evaluation of malignancy.</description><subject>Biopsy</subject><subject>Carcinoma, Pancreatic Ductal - diagnosis</subject><subject>Carcinoma, Pancreatic Ductal - genetics</subject><subject>Carcinoma, Pancreatic Ductal - surgery</subject><subject>Cellular biology</subject><subject>Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods</subject><subject>High-Throughput Nucleotide Sequencing - methods</subject><subject>Humans</subject><subject>liquid‐based cytology</subject><subject>Mutation</subject><subject>next‐generation sequencing</subject><subject>Original</subject><subject>Pancreatic cancer</subject><subject>pancreatic ductal carcinoma</subject><subject>pancreatic lesions</subject><subject>Pancreatic Neoplasms</subject><subject>Pancreatic Neoplasms - diagnosis</subject><subject>Pancreatic Neoplasms - genetics</subject><subject>Pancreatic Neoplasms - pathology</subject><subject>Proto-Oncogene Proteins p21(ras) - genetics</subject><subject>proto‐oncogene proteins p21(ras)</subject><subject>Retrospective Studies</subject><issn>1934-662X</issn><issn>1934-6638</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>24P</sourceid><sourceid>WIN</sourceid><sourceid>EIF</sourceid><recordid>eNp9kcFu1TAQRSMEoqWw4QNQJDYI6ZXYiZ14g4SeCkWq2g1IsLIm9iS4cuxXOylkx54N38iX1GnKE7BgNdbMmevRvVn2lBTHpCjoK-XUfEwpo-xedkhEWW04L5v7-zf9dJA9ivGyKEhTU_IwOygrzpko2WH24-Qa7ASj8S4Hp3NtoHc-jkblywBz3-UOv42_vv_s0WFYyYhXEzplXJ-WwM7RxAUMGI2ewObWXE1Gp50WIupczaO3vp_zuENlBnS39A6cCgjLVwPEiPFx9qADG_HJXT3KPr49-bA93ZxdvHu_fXO2UYxUbKNaolhDao2d0kVRQ1vXohSKdLrmVSt0oVXqsK4RvOUMVMcFdgxY3dYMgJdH2etVdze1A2qFbgxg5S6YAcIsPRj598SZL7L311JQUTcNTQIv7gSCT0bEUQ4mKrQWHPopSsqaKnnNK5LQ5_-gl34KybNE8ZJVVDCyUC9XSgUfY8Bufwwp5JKxXDKWtxkn-Nmf5-_R36EmgKzAV2Nx_o-U3J5vP6-iN5OOuOw</recordid><startdate>202203</startdate><enddate>202203</enddate><creator>Sekita‐Hatakeyama, Yoko</creator><creator>Fujii, Tomomi</creator><creator>Nishikawa, Takeshi</creator><creator>Mitoro, Akira</creator><creator>Sawai, Masayoshi</creator><creator>Itami, Hiroe</creator><creator>Morita, Kouhei</creator><creator>Uchiyama, Tomoko</creator><creator>Takeda, Maiko</creator><creator>Sho, Masayuki</creator><creator>Yoshiji, Hitoshi</creator><creator>Hatakeyama, Kinta</creator><creator>Ohbayashi, Chiho</creator><general>Wiley Subscription Services, Inc</general><general>John Wiley and Sons Inc</general><scope>24P</scope><scope>WIN</scope><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>K9.</scope><scope>7X8</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0001-7729-1836</orcidid><orcidid>https://orcid.org/0000-0002-8046-9508</orcidid></search><sort><creationdate>202203</creationdate><title>Evaluation and diagnostic value of next‐generation sequencing analysis of residual liquid‐based cytology specimens of pancreatic masses</title><author>Sekita‐Hatakeyama, Yoko ; Fujii, Tomomi ; Nishikawa, Takeshi ; Mitoro, Akira ; Sawai, Masayoshi ; Itami, Hiroe ; Morita, Kouhei ; Uchiyama, Tomoko ; Takeda, Maiko ; Sho, Masayuki ; Yoshiji, Hitoshi ; Hatakeyama, Kinta ; Ohbayashi, Chiho</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c5145-cb1c5817defcd007ab77939c1fd764b9d0dc7795f896b65acf69ef5a57b75aa63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Biopsy</topic><topic>Carcinoma, Pancreatic Ductal - diagnosis</topic><topic>Carcinoma, Pancreatic Ductal - genetics</topic><topic>Carcinoma, Pancreatic Ductal - surgery</topic><topic>Cellular biology</topic><topic>Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods</topic><topic>High-Throughput Nucleotide Sequencing - methods</topic><topic>Humans</topic><topic>liquid‐based cytology</topic><topic>Mutation</topic><topic>next‐generation sequencing</topic><topic>Original</topic><topic>Pancreatic cancer</topic><topic>pancreatic ductal carcinoma</topic><topic>pancreatic lesions</topic><topic>Pancreatic Neoplasms</topic><topic>Pancreatic Neoplasms - diagnosis</topic><topic>Pancreatic Neoplasms - genetics</topic><topic>Pancreatic Neoplasms - pathology</topic><topic>Proto-Oncogene Proteins p21(ras) - genetics</topic><topic>proto‐oncogene proteins p21(ras)</topic><topic>Retrospective Studies</topic><toplevel>online_resources</toplevel><creatorcontrib>Sekita‐Hatakeyama, Yoko</creatorcontrib><creatorcontrib>Fujii, Tomomi</creatorcontrib><creatorcontrib>Nishikawa, Takeshi</creatorcontrib><creatorcontrib>Mitoro, Akira</creatorcontrib><creatorcontrib>Sawai, Masayoshi</creatorcontrib><creatorcontrib>Itami, Hiroe</creatorcontrib><creatorcontrib>Morita, Kouhei</creatorcontrib><creatorcontrib>Uchiyama, Tomoko</creatorcontrib><creatorcontrib>Takeda, Maiko</creatorcontrib><creatorcontrib>Sho, Masayuki</creatorcontrib><creatorcontrib>Yoshiji, Hitoshi</creatorcontrib><creatorcontrib>Hatakeyama, Kinta</creatorcontrib><creatorcontrib>Ohbayashi, Chiho</creatorcontrib><collection>Wiley-Blackwell Open Access Titles</collection><collection>Wiley Free Content</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Cancer cytopathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sekita‐Hatakeyama, Yoko</au><au>Fujii, Tomomi</au><au>Nishikawa, Takeshi</au><au>Mitoro, Akira</au><au>Sawai, Masayoshi</au><au>Itami, Hiroe</au><au>Morita, Kouhei</au><au>Uchiyama, Tomoko</au><au>Takeda, Maiko</au><au>Sho, Masayuki</au><au>Yoshiji, Hitoshi</au><au>Hatakeyama, Kinta</au><au>Ohbayashi, Chiho</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Evaluation and diagnostic value of next‐generation sequencing analysis of residual liquid‐based cytology specimens of pancreatic masses</atitle><jtitle>Cancer cytopathology</jtitle><addtitle>Cancer Cytopathol</addtitle><date>2022-03</date><risdate>2022</risdate><volume>130</volume><issue>3</issue><spage>202</spage><epage>214</epage><pages>202-214</pages><issn>1934-662X</issn><eissn>1934-6638</eissn><abstract>Background
Liquid‐based cytology (LBC) is a widely used method for processing specimens obtained by endoscopic biopsy. This study evaluated next‐generation sequencing (NGS) analysis of LBC specimens to improve the diagnostic accuracy of pancreatic lesions.
Methods
Upon the diagnosis of a suspected pancreatic mass, LBC residues were used retrospectively. The quantity and quality of DNA extracted from residual LBC samples were evaluated, and an NGS analysis targeting 6 genes (KRAS, GNAS, TP53, CDKN2A, SMAD4, and PIK3CA) was performed.
Results
The library was prepared from LBC specimens taken from 52 cases: 44 were successful, and 8 preparations failed. An analysis of DNA quantity and quality suggested that the success or failure of NGS implementation depended on both properties. The final diagnosis was achieved by a combination of the pathological analysis of the surgical excision or biopsy material with clinical information. Among the 33 cases of pancreatic ductal adenocarcinoma (PDAC), KRAS, TP53, CDKN2A, and SMAD4 mutations were identified in 31 (94%), 16 (48%), 3 (9%), and 2 (6%), respectively. Among the 11 benign cases, only a KRAS mutation was identified in 1 case. On the basis of NGS results, 18 of 33 PDACs (55%) were classified as highly dysplastic or more, and 10 of 11 benign lesions were evaluated as nonmalignant, which was consistent with the final diagnosis.
Conclusions
NGS analysis using LBC specimens from which DNA of appropriate quantity and quality has been extracted could contribute to improving the assessment of pancreatic tumor malignancies and the application of molecular‐targeted drugs.
This article presents the feasibility of using a next‐generation sequencing (NGS) assay for liquid‐based cytology (LBC) specimens with DNA of sufficient quantity and quality. The detection of cancer‐related mutations by NGS using LBC demonstrates its value for the evaluation of malignancy.</abstract><cop>United States</cop><pub>Wiley Subscription Services, Inc</pub><pmid>34665935</pmid><doi>10.1002/cncy.22525</doi><tpages>13</tpages><orcidid>https://orcid.org/0000-0001-7729-1836</orcidid><orcidid>https://orcid.org/0000-0002-8046-9508</orcidid><oa>free_for_read</oa></addata></record> |
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subjects | Biopsy Carcinoma, Pancreatic Ductal - diagnosis Carcinoma, Pancreatic Ductal - genetics Carcinoma, Pancreatic Ductal - surgery Cellular biology Endoscopic Ultrasound-Guided Fine Needle Aspiration - methods High-Throughput Nucleotide Sequencing - methods Humans liquid‐based cytology Mutation next‐generation sequencing Original Pancreatic cancer pancreatic ductal carcinoma pancreatic lesions Pancreatic Neoplasms Pancreatic Neoplasms - diagnosis Pancreatic Neoplasms - genetics Pancreatic Neoplasms - pathology Proto-Oncogene Proteins p21(ras) - genetics proto‐oncogene proteins p21(ras) Retrospective Studies |
title | Evaluation and diagnostic value of next‐generation sequencing analysis of residual liquid‐based cytology specimens of pancreatic masses |
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