MUC4 is increased in high grade intraepithelial neoplasia in Barrett’s oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio

Background: Patients with Barrett’s oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. Aims: To determine the expression pattern of mucins in neoplastic BO epit...

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Published in:Journal of clinical pathology 2004-12, Vol.57 (12), p.1267-1272
Main Authors: Bax, D A, Haringsma, J, Einerhand, A W C, van Dekken, H, Blok, P, Siersema, P D, Kuipers, E J, Kusters, J G
Format: Article
Language:English
Subjects:
ADC
adenocarcinoma
Adenocarcinoma - chemistry
alkaline phosphatase
Apoptosis
Apoptosis - physiology
Barrett Esophagus - metabolism
Barrett’s oesophagus
bcl-2-Associated X Protein
Biopsy
Carcinoma in Situ - chemistry
Cell adhesion & migration
Cell cycle
Endoscopy
Esophageal Neoplasms - chemistry
Gene Expression Regulation, Neoplastic
HGN
high grade dysplasia
high grade intraepithelial neoplasia
Humans
Hypotheses
Ligands
Medical prognosis
Mucin-4
mucins
Mucins - analysis
Neoplasm Proteins - analysis
Original
PCR
polymerase chain reaction
Proteins
Proto-Oncogene Proteins c-bcl-2 - analysis
Reverse Transcriptase Polymerase Chain Reaction - methods
reverse transcription
RNA, Messenger - analysis
RNA, Neoplasm - analysis
Studies
Surveillance
Tumors
tumour markers
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cited_by cdi_FETCH-LOGICAL-b523t-2bd94901590f1b21fb8f241917148befadd9ebb88f338307feab2eb43e9a43253
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container_end_page 1272
container_issue 12
container_start_page 1267
container_title Journal of clinical pathology
container_volume 57
creator Bax, D A
Haringsma, J
Einerhand, A W C
van Dekken, H
Blok, P
Siersema, P D
Kuipers, E J
Kusters, J G
description Background: Patients with Barrett’s oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. Aims: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. Methods: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett’s epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1–4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. Results: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p
doi_str_mv 10.1136/jcp.2004.017020
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Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. Aims: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. Methods: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett’s epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1–4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. Results: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p&lt;0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. Conclusions: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.</description><identifier>ISSN: 0021-9746</identifier><identifier>EISSN: 1472-4146</identifier><identifier>DOI: 10.1136/jcp.2004.017020</identifier><identifier>PMID: 15563666</identifier><identifier>CODEN: JCPAAK</identifier><language>eng</language><publisher>England: BMJ Publishing Group Ltd and Association of Clinical Pathologists</publisher><subject>ADC ; adenocarcinoma ; Adenocarcinoma - chemistry ; alkaline phosphatase ; Apoptosis ; Apoptosis - physiology ; Barrett Esophagus - metabolism ; Barrett’s oesophagus ; bcl-2-Associated X Protein ; Biopsy ; Carcinoma in Situ - chemistry ; Cell adhesion &amp; migration ; Cell cycle ; Endoscopy ; Esophageal Neoplasms - chemistry ; Gene Expression Regulation, Neoplastic ; HGN ; high grade dysplasia ; high grade intraepithelial neoplasia ; Humans ; Hypotheses ; Ligands ; Medical prognosis ; Mucin-4 ; mucins ; Mucins - analysis ; Neoplasm Proteins - analysis ; Original ; PCR ; polymerase chain reaction ; Proteins ; Proto-Oncogene Proteins c-bcl-2 - analysis ; Reverse Transcriptase Polymerase Chain Reaction - methods ; reverse transcription ; RNA, Messenger - analysis ; RNA, Neoplasm - analysis ; Studies ; Surveillance ; Tumors ; tumour markers</subject><ispartof>Journal of clinical pathology, 2004-12, Vol.57 (12), p.1267-1272</ispartof><rights>Copyright 2004 Journal of Clinical Pathology</rights><rights>Copyright: 2004 Copyright 2004 Journal of Clinical Pathology</rights><rights>Copyright © Copyright 2004 Journal of Clinical Pathology 2004</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b523t-2bd94901590f1b21fb8f241917148befadd9ebb88f338307feab2eb43e9a43253</citedby><cites>FETCH-LOGICAL-b523t-2bd94901590f1b21fb8f241917148befadd9ebb88f338307feab2eb43e9a43253</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770513/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1770513/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/15563666$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Bax, D A</creatorcontrib><creatorcontrib>Haringsma, J</creatorcontrib><creatorcontrib>Einerhand, A W C</creatorcontrib><creatorcontrib>van Dekken, H</creatorcontrib><creatorcontrib>Blok, P</creatorcontrib><creatorcontrib>Siersema, P D</creatorcontrib><creatorcontrib>Kuipers, E J</creatorcontrib><creatorcontrib>Kusters, J G</creatorcontrib><title>MUC4 is increased in high grade intraepithelial neoplasia in Barrett’s oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio</title><title>Journal of clinical pathology</title><addtitle>J Clin Pathol</addtitle><description>Background: Patients with Barrett’s oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. Aims: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. Methods: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett’s epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1–4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. Results: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p&lt;0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. Conclusions: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.</description><subject>ADC</subject><subject>adenocarcinoma</subject><subject>Adenocarcinoma - chemistry</subject><subject>alkaline phosphatase</subject><subject>Apoptosis</subject><subject>Apoptosis - physiology</subject><subject>Barrett Esophagus - metabolism</subject><subject>Barrett’s oesophagus</subject><subject>bcl-2-Associated X Protein</subject><subject>Biopsy</subject><subject>Carcinoma in Situ - chemistry</subject><subject>Cell adhesion &amp; migration</subject><subject>Cell cycle</subject><subject>Endoscopy</subject><subject>Esophageal Neoplasms - chemistry</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>HGN</subject><subject>high grade dysplasia</subject><subject>high grade intraepithelial neoplasia</subject><subject>Humans</subject><subject>Hypotheses</subject><subject>Ligands</subject><subject>Medical prognosis</subject><subject>Mucin-4</subject><subject>mucins</subject><subject>Mucins - analysis</subject><subject>Neoplasm Proteins - analysis</subject><subject>Original</subject><subject>PCR</subject><subject>polymerase chain reaction</subject><subject>Proteins</subject><subject>Proto-Oncogene Proteins c-bcl-2 - analysis</subject><subject>Reverse Transcriptase Polymerase Chain Reaction - methods</subject><subject>reverse transcription</subject><subject>RNA, Messenger - analysis</subject><subject>RNA, Neoplasm - analysis</subject><subject>Studies</subject><subject>Surveillance</subject><subject>Tumors</subject><subject>tumour markers</subject><issn>0021-9746</issn><issn>1472-4146</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2004</creationdate><recordtype>article</recordtype><recordid>eNqFks1u1DAUhSMEotPCmh2yhMSiUqa-thMnGyQa8ScKqFIL7KzrxJnxkBkH2wNlxwPwArweT4KjGZWfTVe2db97fM_VybIHQOcAvDxZteOcUSrmFCRl9FY2AyFZLkCUt7MZpQzyWoryIDsMYUUpcAn8bnYARVHysixn2Y83l40gNhC7ab3BYLp0I0u7WJKFx86kV_RoRhuXZrA4kI1x44DB4sSdovcmxl_ffwbiTHDjEhfbQHDTTZIYgmstxqT5NfUTJKN3OLoxumjb1HxFoiOn7ZAz4jFady-70-MQzP39eZRdPn920bzMz969eNU8Pct1wXjMme5qUVMoatqDZtDrqmcCapAgKm167LraaF1VPecVp7I3qJnRgpsaBWcFP8qe7HTHrV6brjWTx0GN3q7Rf1MOrfq3srFLtXBfFEhJC-BJ4PFewLvPWxOiWtvQmmHAtJ5tUKWEtHpxMwiS1RWT00iP_gNXbus3aQuJqZKaSFCiTnZU610I3vTXMwNVUyBUCoSaAqF2gUgdD_-2-offJyAB-Q6wIZqr6zr6T8kFl4V6-75RxYfm4lx8fK3OE3-84_V6dePvvwFJjdAk</recordid><startdate>200412</startdate><enddate>200412</enddate><creator>Bax, D A</creator><creator>Haringsma, J</creator><creator>Einerhand, A W C</creator><creator>van Dekken, H</creator><creator>Blok, P</creator><creator>Siersema, P D</creator><creator>Kuipers, E J</creator><creator>Kusters, J G</creator><general>BMJ Publishing Group Ltd and Association of Clinical Pathologists</general><general>BMJ Publishing Group LTD</general><general>Copyright 2004 Journal of Clinical Pathology</general><scope>BSCLL</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>88I</scope><scope>8AF</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>Q9U</scope><scope>7TO</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>200412</creationdate><title>MUC4 is increased in high grade intraepithelial neoplasia in Barrett’s oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio</title><author>Bax, D A ; Haringsma, J ; Einerhand, A W C ; van Dekken, H ; Blok, P ; Siersema, P D ; Kuipers, E J ; Kusters, J G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b523t-2bd94901590f1b21fb8f241917148befadd9ebb88f338307feab2eb43e9a43253</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2004</creationdate><topic>ADC</topic><topic>adenocarcinoma</topic><topic>Adenocarcinoma - chemistry</topic><topic>alkaline phosphatase</topic><topic>Apoptosis</topic><topic>Apoptosis - physiology</topic><topic>Barrett Esophagus - metabolism</topic><topic>Barrett’s oesophagus</topic><topic>bcl-2-Associated X Protein</topic><topic>Biopsy</topic><topic>Carcinoma in Situ - chemistry</topic><topic>Cell adhesion &amp; migration</topic><topic>Cell cycle</topic><topic>Endoscopy</topic><topic>Esophageal Neoplasms - chemistry</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>HGN</topic><topic>high grade dysplasia</topic><topic>high grade intraepithelial neoplasia</topic><topic>Humans</topic><topic>Hypotheses</topic><topic>Ligands</topic><topic>Medical prognosis</topic><topic>Mucin-4</topic><topic>mucins</topic><topic>Mucins - analysis</topic><topic>Neoplasm Proteins - analysis</topic><topic>Original</topic><topic>PCR</topic><topic>polymerase chain reaction</topic><topic>Proteins</topic><topic>Proto-Oncogene Proteins c-bcl-2 - analysis</topic><topic>Reverse Transcriptase Polymerase Chain Reaction - methods</topic><topic>reverse transcription</topic><topic>RNA, Messenger - analysis</topic><topic>RNA, Neoplasm - analysis</topic><topic>Studies</topic><topic>Surveillance</topic><topic>Tumors</topic><topic>tumour markers</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Bax, D A</creatorcontrib><creatorcontrib>Haringsma, J</creatorcontrib><creatorcontrib>Einerhand, A W C</creatorcontrib><creatorcontrib>van Dekken, H</creatorcontrib><creatorcontrib>Blok, P</creatorcontrib><creatorcontrib>Siersema, P D</creatorcontrib><creatorcontrib>Kuipers, E J</creatorcontrib><creatorcontrib>Kusters, J G</creatorcontrib><collection>Istex</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 Central (Corporate)</collection><collection>Health &amp; 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Medical Complete (Alumni)</collection><collection>Health &amp; Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>ProQuest Science Journals</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>ProQuest Central Basic</collection><collection>Oncogenes and Growth Factors Abstracts</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of clinical pathology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Bax, D A</au><au>Haringsma, J</au><au>Einerhand, A W C</au><au>van Dekken, H</au><au>Blok, P</au><au>Siersema, P D</au><au>Kuipers, E J</au><au>Kusters, J G</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>MUC4 is increased in high grade intraepithelial neoplasia in Barrett’s oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio</atitle><jtitle>Journal of clinical pathology</jtitle><addtitle>J Clin Pathol</addtitle><date>2004-12</date><risdate>2004</risdate><volume>57</volume><issue>12</issue><spage>1267</spage><epage>1272</epage><pages>1267-1272</pages><issn>0021-9746</issn><eissn>1472-4146</eissn><coden>JCPAAK</coden><abstract>Background: Patients with Barrett’s oesophagus (BO) are at risk of oesophageal adenocarcinoma. Because the pattern of mucosal mucins changes during neoplastic progression, it may serve as a marker of intraepithelial neoplasia. Aims: To determine the expression pattern of mucins in neoplastic BO epithelium (high grade dysplasia) and correlate it with the expression of apoptosis markers Bax and Bcl-2. Methods: Thirty seven patients with BO were studied: 16 without intraepithelial neoplasia, six with high grade intraepithelial neoplasia (HGN), and 15 with infiltrating adenocarcinoma. Biopsies were obtained from squamous epithelium, Barrett’s epithelium, and (when present) foci of suspected HGN or adenocarcinoma. MUC1–4, MUC5AC, MUC5B, MUC6, Bax, and Bcl-2 mRNA were determined by semiquantitative RT-PCR. MUC2, MUC5AC, and MUC6 protein was determined by immunoblotting. Results: Mucin expression varied between neoplastic progression stages in BO. Mucin mRNA levels were low in squamous epithelium, except for MUC4, and were at least four times higher in BO and HGN (p&lt;0.001), but less so in adenocarcinoma. MUC4 expression was significantly lower in BO than in normal squamous epithelium, whereas in HGN and adenocarcinoma, levels were significantly higher than in BO (p = 0.037). The Bax:Bcl-2 ratio was increased in HGN compared with BO (p = 0.04). MUC2, MUC5AC, and MUC6 protein values correlated with mRNA data. Conclusions: Mucin expression varies during the development of oesophageal adenocarcinoma in BO. MUC4 could serve as a tumour marker in this process. In contrast to animal studies, upregulation of MUC4 in HGN is associated with increased apoptosis, suggesting that MUC4 plays a minor role in apoptosis regulation in BO.</abstract><cop>England</cop><pub>BMJ Publishing Group Ltd and Association of Clinical Pathologists</pub><pmid>15563666</pmid><doi>10.1136/jcp.2004.017020</doi><tpages>6</tpages><oa>free_for_read</oa></addata></record>
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subjects ADC
adenocarcinoma
Adenocarcinoma - chemistry
alkaline phosphatase
Apoptosis
Apoptosis - physiology
Barrett Esophagus - metabolism
Barrett’s oesophagus
bcl-2-Associated X Protein
Biopsy
Carcinoma in Situ - chemistry
Cell adhesion & migration
Cell cycle
Endoscopy
Esophageal Neoplasms - chemistry
Gene Expression Regulation, Neoplastic
HGN
high grade dysplasia
high grade intraepithelial neoplasia
Humans
Hypotheses
Ligands
Medical prognosis
Mucin-4
mucins
Mucins - analysis
Neoplasm Proteins - analysis
Original
PCR
polymerase chain reaction
Proteins
Proto-Oncogene Proteins c-bcl-2 - analysis
Reverse Transcriptase Polymerase Chain Reaction - methods
reverse transcription
RNA, Messenger - analysis
RNA, Neoplasm - analysis
Studies
Surveillance
Tumors
tumour markers
title MUC4 is increased in high grade intraepithelial neoplasia in Barrett’s oesophagus and is associated with a proapoptotic Bax to Bcl-2 ratio
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