Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett’s Esophagus-Related Neoplasia: A Feasibility Study

Background The endoscopic detection of esophageal cancer is suboptimal in both patients referred with dyspeptic symptoms and those enrolled in Barrett’s surveillance programs. MCM5 expression in cells collected from gastric fluid may be correlated with the presence of dysplasia or adenocarcinoma. An...

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Veröffentlicht in:Digestive diseases and sciences 2019-10, Vol.64 (10), p.2815-2822
Hauptverfasser: Everson, M., Magee, C., Alzoubaidi, D., Brogden, S., Graham, D., Lovat, L. B., Novelli, M., Haidry, R.
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container_end_page 2822
container_issue 10
container_start_page 2815
container_title Digestive diseases and sciences
container_volume 64
creator Everson, M.
Magee, C.
Alzoubaidi, D.
Brogden, S.
Graham, D.
Lovat, L. B.
Novelli, M.
Haidry, R.
description Background The endoscopic detection of esophageal cancer is suboptimal in both patients referred with dyspeptic symptoms and those enrolled in Barrett’s surveillance programs. MCM5 expression in cells collected from gastric fluid may be correlated with the presence of dysplasia or adenocarcinoma. Analysis of this biomarker may improve the detection of cancer. Methods Sixty-one patients were enrolled at a single UK referral center. From each patient, 5–10 ml of gastric fluid was aspirated endoscopically. Patients were categorized according to their histology, normal, non-dysplastic Barrett’s (NDBE), high-grade dysplastic Barrett’s (HGD), and esophageal adenocarcinoma (EAC). All histology was confirmed by Seattle protocol biopsies or endoscopic mucosal resection. Samples were centrifuged, and the cell pellet was lysed. MCM5 expression levels were quantified using a proprietary immunoassay. The mean MCM5 expression was compared between groups by Kruskal–Wallis test. ROC curves were also used to assess diagnostic utility. Results The mean expression of MCM5 increases as patients progress from a normal esophagus to NDBE, HGD, and EAC (14.4; 49.8; 112.3; and 154.1, respectively). There was a significant difference in the MCM5 expression of patients with a normal esophagus compared to those with EAC ( p  = 0.04). There was a trend toward higher MCM5 expression in patients with EAC compared to those with NDBE ( p  = 0.34). MCM5 expression was a fair discriminator (AUC 0.70 [95% CI 0.57–0.83]) between patients without neoplasia (normal and NDBE) and those with early neoplasia (HGD and EAC). Conclusion MCM5 expression in gastric fluid samples can differentiate patients with a histologically normal esophagus compared to those with early adenocarcinoma. Larger, powered studies are needed to assess whether it can be used to differentiate those with HGD from NDBE.
doi_str_mv 10.1007/s10620-019-05607-5
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Samples were centrifuged, and the cell pellet was lysed. MCM5 expression levels were quantified using a proprietary immunoassay. The mean MCM5 expression was compared between groups by Kruskal–Wallis test. ROC curves were also used to assess diagnostic utility. Results The mean expression of MCM5 increases as patients progress from a normal esophagus to NDBE, HGD, and EAC (14.4; 49.8; 112.3; and 154.1, respectively). There was a significant difference in the MCM5 expression of patients with a normal esophagus compared to those with EAC ( p  = 0.04). There was a trend toward higher MCM5 expression in patients with EAC compared to those with NDBE ( p  = 0.34). MCM5 expression was a fair discriminator (AUC 0.70 [95% CI 0.57–0.83]) between patients without neoplasia (normal and NDBE) and those with early neoplasia (HGD and EAC). Conclusion MCM5 expression in gastric fluid samples can differentiate patients with a histologically normal esophagus compared to those with early adenocarcinoma. Larger, powered studies are needed to assess whether it can be used to differentiate those with HGD from NDBE.</description><identifier>ISSN: 0163-2116</identifier><identifier>EISSN: 1573-2568</identifier><identifier>DOI: 10.1007/s10620-019-05607-5</identifier><identifier>PMID: 30982210</identifier><language>eng</language><publisher>New York: Springer US</publisher><subject>Adenocarcinoma - diagnosis ; Adenocarcinoma - metabolism ; Adenocarcinoma - pathology ; Barrett Esophagus - diagnosis ; Barrett Esophagus - metabolism ; Barrett Esophagus - pathology ; Biochemistry ; Biomarkers ; Biomarkers - analysis ; Biopsy - methods ; Cancer ; Cell Cycle Proteins - analysis ; Cost analysis ; Deoxyribonucleic acid ; Diagnosis ; Disease Progression ; DNA ; DNA Replication ; Dysplasia ; Early Detection of Cancer - methods ; Endoscopy ; Endoscopy, Digestive System - methods ; Esophageal cancer ; Esophageal Neoplasms - diagnosis ; Esophageal Neoplasms - metabolism ; Esophageal Neoplasms - pathology ; Feasibility Studies ; Female ; Gastric Juice - metabolism ; Gastroenterology ; Hepatology ; Histology ; Humans ; Immunoassay ; Male ; Medicine ; Medicine &amp; Public Health ; Middle Aged ; Oncology ; Original Article ; Pathology ; Patients ; Precancerous Conditions - diagnosis ; Precancerous Conditions - metabolism ; Precancerous Conditions - pathology ; Proteins ; Surveillance ; Systematic review ; Transplant Surgery ; University colleges ; Urine</subject><ispartof>Digestive diseases and sciences, 2019-10, Vol.64 (10), p.2815-2822</ispartof><rights>Springer Science+Business Media, LLC, part of Springer Nature 2019</rights><rights>COPYRIGHT 2019 Springer</rights><rights>Digestive Diseases and Sciences is a copyright of Springer, (2019). All Rights Reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c486t-b69e4f1558af2724b77d2ecb764d36ee43ff800b3e72884d6987751ab5fde1413</citedby><cites>FETCH-LOGICAL-c486t-b69e4f1558af2724b77d2ecb764d36ee43ff800b3e72884d6987751ab5fde1413</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s10620-019-05607-5$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s10620-019-05607-5$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,776,780,27901,27902,41464,42533,51294</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/30982210$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Everson, M.</creatorcontrib><creatorcontrib>Magee, C.</creatorcontrib><creatorcontrib>Alzoubaidi, D.</creatorcontrib><creatorcontrib>Brogden, S.</creatorcontrib><creatorcontrib>Graham, D.</creatorcontrib><creatorcontrib>Lovat, L. B.</creatorcontrib><creatorcontrib>Novelli, M.</creatorcontrib><creatorcontrib>Haidry, R.</creatorcontrib><title>Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett’s Esophagus-Related Neoplasia: A Feasibility Study</title><title>Digestive diseases and sciences</title><addtitle>Dig Dis Sci</addtitle><addtitle>Dig Dis Sci</addtitle><description>Background The endoscopic detection of esophageal cancer is suboptimal in both patients referred with dyspeptic symptoms and those enrolled in Barrett’s surveillance programs. MCM5 expression in cells collected from gastric fluid may be correlated with the presence of dysplasia or adenocarcinoma. Analysis of this biomarker may improve the detection of cancer. Methods Sixty-one patients were enrolled at a single UK referral center. From each patient, 5–10 ml of gastric fluid was aspirated endoscopically. Patients were categorized according to their histology, normal, non-dysplastic Barrett’s (NDBE), high-grade dysplastic Barrett’s (HGD), and esophageal adenocarcinoma (EAC). All histology was confirmed by Seattle protocol biopsies or endoscopic mucosal resection. Samples were centrifuged, and the cell pellet was lysed. MCM5 expression levels were quantified using a proprietary immunoassay. The mean MCM5 expression was compared between groups by Kruskal–Wallis test. ROC curves were also used to assess diagnostic utility. Results The mean expression of MCM5 increases as patients progress from a normal esophagus to NDBE, HGD, and EAC (14.4; 49.8; 112.3; and 154.1, respectively). There was a significant difference in the MCM5 expression of patients with a normal esophagus compared to those with EAC ( p  = 0.04). There was a trend toward higher MCM5 expression in patients with EAC compared to those with NDBE ( p  = 0.34). MCM5 expression was a fair discriminator (AUC 0.70 [95% CI 0.57–0.83]) between patients without neoplasia (normal and NDBE) and those with early neoplasia (HGD and EAC). Conclusion MCM5 expression in gastric fluid samples can differentiate patients with a histologically normal esophagus compared to those with early adenocarcinoma. Larger, powered studies are needed to assess whether it can be used to differentiate those with HGD from NDBE.</description><subject>Adenocarcinoma - diagnosis</subject><subject>Adenocarcinoma - metabolism</subject><subject>Adenocarcinoma - pathology</subject><subject>Barrett Esophagus - diagnosis</subject><subject>Barrett Esophagus - metabolism</subject><subject>Barrett Esophagus - pathology</subject><subject>Biochemistry</subject><subject>Biomarkers</subject><subject>Biomarkers - analysis</subject><subject>Biopsy - methods</subject><subject>Cancer</subject><subject>Cell Cycle Proteins - analysis</subject><subject>Cost analysis</subject><subject>Deoxyribonucleic acid</subject><subject>Diagnosis</subject><subject>Disease Progression</subject><subject>DNA</subject><subject>DNA Replication</subject><subject>Dysplasia</subject><subject>Early Detection of Cancer - methods</subject><subject>Endoscopy</subject><subject>Endoscopy, Digestive System - methods</subject><subject>Esophageal cancer</subject><subject>Esophageal Neoplasms - diagnosis</subject><subject>Esophageal Neoplasms - metabolism</subject><subject>Esophageal Neoplasms - pathology</subject><subject>Feasibility Studies</subject><subject>Female</subject><subject>Gastric Juice - metabolism</subject><subject>Gastroenterology</subject><subject>Hepatology</subject><subject>Histology</subject><subject>Humans</subject><subject>Immunoassay</subject><subject>Male</subject><subject>Medicine</subject><subject>Medicine &amp; Public Health</subject><subject>Middle Aged</subject><subject>Oncology</subject><subject>Original Article</subject><subject>Pathology</subject><subject>Patients</subject><subject>Precancerous Conditions - diagnosis</subject><subject>Precancerous Conditions - metabolism</subject><subject>Precancerous Conditions - pathology</subject><subject>Proteins</subject><subject>Surveillance</subject><subject>Systematic review</subject><subject>Transplant Surgery</subject><subject>University colleges</subject><subject>Urine</subject><issn>0163-2116</issn><issn>1573-2568</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2019</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNp9kc1u1DAUhS0EokPhBVggS2zKIsV2YjthN4xaQOqAxM_acpLrqUtip7YjMbuqb8Hr8SR4OoUKhJAXvnK-c3RzDkJPKTmmhMiXkRLBSEFoUxAuiCz4PbSgXJYF46K-jxaEijxTKg7QoxgvCCGNpOIhOihJUzNGyQJdr62z3Xnwo49-1ANea-sSOO06wCs_Tt6BSzfTAN8wx0fr1Zq_wDpindnwFQL2Br_WIUBKP66-R3wS_XSuN3MsPsKgE_T4Pfhp0NHqV3iJTyFPrR1s2uJPae63j9EDo4cIT27vQ_Tl9OTz6m1x9uHNu9XyrOiqWqSiFQ1UhnJea8Mkq1opewZdK0XVlwKgKo2pCWlLkKyuq140tZSc6pabHmhFy0N0tPedgr-cISY12tjBMGgHfo5qF0iOlfEyo8__Qi_8HFzeLlOkoTnyWtxRGz2Ass74FHS3M1VLSVlTCkl2Xsf_oPLpYbRdjtfY_P6HgO0FXfAxBjBqCnbUYasoUbvi1b54lbdQN8UrnkXPbjee2xH635JfTWeg3AMxf3IbCHe_9B_bn_uStts</recordid><startdate>20191001</startdate><enddate>20191001</enddate><creator>Everson, M.</creator><creator>Magee, C.</creator><creator>Alzoubaidi, D.</creator><creator>Brogden, S.</creator><creator>Graham, D.</creator><creator>Lovat, L. 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B.</creatorcontrib><creatorcontrib>Novelli, M.</creatorcontrib><creatorcontrib>Haidry, R.</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Nursing &amp; Allied Health Database</collection><collection>Health &amp; Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>ProQuest Pharma Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>Consumer Health Database (Alumni Edition)</collection><collection>ProQuest Health &amp; Medical Complete (Alumni)</collection><collection>Nursing &amp; Allied Health Database (Alumni Edition)</collection><collection>Consumer Health Database</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Nursing &amp; Allied Health Premium</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><jtitle>Digestive diseases and sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Everson, M.</au><au>Magee, C.</au><au>Alzoubaidi, D.</au><au>Brogden, S.</au><au>Graham, D.</au><au>Lovat, L. B.</au><au>Novelli, M.</au><au>Haidry, R.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett’s Esophagus-Related Neoplasia: A Feasibility Study</atitle><jtitle>Digestive diseases and sciences</jtitle><stitle>Dig Dis Sci</stitle><addtitle>Dig Dis Sci</addtitle><date>2019-10-01</date><risdate>2019</risdate><volume>64</volume><issue>10</issue><spage>2815</spage><epage>2822</epage><pages>2815-2822</pages><issn>0163-2116</issn><eissn>1573-2568</eissn><abstract>Background The endoscopic detection of esophageal cancer is suboptimal in both patients referred with dyspeptic symptoms and those enrolled in Barrett’s surveillance programs. MCM5 expression in cells collected from gastric fluid may be correlated with the presence of dysplasia or adenocarcinoma. Analysis of this biomarker may improve the detection of cancer. Methods Sixty-one patients were enrolled at a single UK referral center. From each patient, 5–10 ml of gastric fluid was aspirated endoscopically. Patients were categorized according to their histology, normal, non-dysplastic Barrett’s (NDBE), high-grade dysplastic Barrett’s (HGD), and esophageal adenocarcinoma (EAC). All histology was confirmed by Seattle protocol biopsies or endoscopic mucosal resection. Samples were centrifuged, and the cell pellet was lysed. MCM5 expression levels were quantified using a proprietary immunoassay. The mean MCM5 expression was compared between groups by Kruskal–Wallis test. ROC curves were also used to assess diagnostic utility. Results The mean expression of MCM5 increases as patients progress from a normal esophagus to NDBE, HGD, and EAC (14.4; 49.8; 112.3; and 154.1, respectively). There was a significant difference in the MCM5 expression of patients with a normal esophagus compared to those with EAC ( p  = 0.04). There was a trend toward higher MCM5 expression in patients with EAC compared to those with NDBE ( p  = 0.34). MCM5 expression was a fair discriminator (AUC 0.70 [95% CI 0.57–0.83]) between patients without neoplasia (normal and NDBE) and those with early neoplasia (HGD and EAC). Conclusion MCM5 expression in gastric fluid samples can differentiate patients with a histologically normal esophagus compared to those with early adenocarcinoma. Larger, powered studies are needed to assess whether it can be used to differentiate those with HGD from NDBE.</abstract><cop>New York</cop><pub>Springer US</pub><pmid>30982210</pmid><doi>10.1007/s10620-019-05607-5</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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subjects Adenocarcinoma - diagnosis
Adenocarcinoma - metabolism
Adenocarcinoma - pathology
Barrett Esophagus - diagnosis
Barrett Esophagus - metabolism
Barrett Esophagus - pathology
Biochemistry
Biomarkers
Biomarkers - analysis
Biopsy - methods
Cancer
Cell Cycle Proteins - analysis
Cost analysis
Deoxyribonucleic acid
Diagnosis
Disease Progression
DNA
DNA Replication
Dysplasia
Early Detection of Cancer - methods
Endoscopy
Endoscopy, Digestive System - methods
Esophageal cancer
Esophageal Neoplasms - diagnosis
Esophageal Neoplasms - metabolism
Esophageal Neoplasms - pathology
Feasibility Studies
Female
Gastric Juice - metabolism
Gastroenterology
Hepatology
Histology
Humans
Immunoassay
Male
Medicine
Medicine & Public Health
Middle Aged
Oncology
Original Article
Pathology
Patients
Precancerous Conditions - diagnosis
Precancerous Conditions - metabolism
Precancerous Conditions - pathology
Proteins
Surveillance
Systematic review
Transplant Surgery
University colleges
Urine
title Minichromosomal Maintenance Component Complex 5 (MCM5) as a Marker of Barrett’s Esophagus-Related Neoplasia: A Feasibility Study
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