Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation

Abstract BACKGROUND : Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P an...

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Published in:Translational oncology 2014-08, Vol.7 (4), p.456-463
Main Authors: Caruso, Maria, Fung, Kim Y.C, Moore, James, Brierley, Gemma V, Cosgrove, Leah J, Thomas, Michelle, Cheetham, Glenice, Brook, Emma, Fraser, Louise M, Tin, Teresa, Tran, Ha, Ruszkiewicz, Andrew
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Oncology
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container_title Translational oncology
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creator Caruso, Maria
Fung, Kim Y.C
Moore, James
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Cheetham, Glenice
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Fraser, Louise M
Tin, Teresa
Tran, Ha
Ruszkiewicz, Andrew
description Abstract BACKGROUND : Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P and microvesicular hyperplastic polyps (MVHP) is challenging and may not be possible in routine practice. METHODS : Gene expression profiling of MVHP ( n =5, all BRAF V600E wild-type ) and SSA/P ( n =5, all BRAF V600E mutant) samples was performed. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunohistochemical analysis was performed to verify the expression of claudin 1 (CLDN1) in MVHP and SSA/P. RESULTS : Gene expression profiling studies conducted between MVHP and SSA/P identified CLDN1 as the most statistically significant differentially expressed gene ( p
doi_str_mv 10.1016/j.tranon.2014.05.009
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While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P and microvesicular hyperplastic polyps (MVHP) is challenging and may not be possible in routine practice. METHODS : Gene expression profiling of MVHP ( n =5, all BRAF V600E wild-type ) and SSA/P ( n =5, all BRAF V600E mutant) samples was performed. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunohistochemical analysis was performed to verify the expression of claudin 1 (CLDN1) in MVHP and SSA/P. RESULTS : Gene expression profiling studies conducted between MVHP and SSA/P identified CLDN1 as the most statistically significant differentially expressed gene ( p &lt;0.05). Validation with qRT-PCR confirmed an up-regulation of CLDN1 in BRAF V600E mutant polyps regardless of polyp type ( p &lt;0.0005). Immunohistochemical analysis of CLDN1 expression in BRAF V600E mutant SSA/Ps ( n =53) and MVHPs ( n =111) and BRAF wild-type MVHPs ( n =58), demonstrated a strong correlation between CLDN1 expression and the BRAF V600E mutation in both SSA/P and MVHP samples when compared to wild-type polyps ( p &lt;0.0001). CONCLUSION : This study demonstrates an up regulation of CLDN1 protein in serrated colorectal polyps including MVHP harbouring the BRAF V600E mutation. Our results demonstrated an apparent heterogeneity on the molecular level within the MVHP group and suggest that MVHP with somatic BRAF V600E mutation and up-regulated expression of CLDN1 are closely related to SSA/P and may in fact represent a continuous spectrum of the same neoplastic process within the serrated pathway of colorectal carcinogenesis.</description><identifier>ISSN: 1936-5233</identifier><identifier>EISSN: 1944-7124</identifier><identifier>DOI: 10.1016/j.tranon.2014.05.009</identifier><identifier>PMID: 24954356</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Oncology</subject><ispartof>Translational oncology, 2014-08, Vol.7 (4), p.456-463</ispartof><rights>2014</rights><rights>Crown Copyright © 2014. Published by Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c529t-288fd816c5897fdb3fb6cb2e7580bfaedc9515a7be6e01ba1e37dd26f856e06c3</citedby><cites>FETCH-LOGICAL-c529t-288fd816c5897fdb3fb6cb2e7580bfaedc9515a7be6e01ba1e37dd26f856e06c3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S1936523314000643$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>314,780,784,3547,27922,27923,45778</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24954356$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Caruso, Maria</creatorcontrib><creatorcontrib>Fung, Kim Y.C</creatorcontrib><creatorcontrib>Moore, James</creatorcontrib><creatorcontrib>Brierley, Gemma V</creatorcontrib><creatorcontrib>Cosgrove, Leah J</creatorcontrib><creatorcontrib>Thomas, Michelle</creatorcontrib><creatorcontrib>Cheetham, Glenice</creatorcontrib><creatorcontrib>Brook, Emma</creatorcontrib><creatorcontrib>Fraser, Louise M</creatorcontrib><creatorcontrib>Tin, Teresa</creatorcontrib><creatorcontrib>Tran, Ha</creatorcontrib><creatorcontrib>Ruszkiewicz, Andrew</creatorcontrib><title>Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation</title><title>Translational oncology</title><addtitle>Transl Oncol</addtitle><description>Abstract BACKGROUND : Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P and microvesicular hyperplastic polyps (MVHP) is challenging and may not be possible in routine practice. METHODS : Gene expression profiling of MVHP ( n =5, all BRAF V600E wild-type ) and SSA/P ( n =5, all BRAF V600E mutant) samples was performed. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunohistochemical analysis was performed to verify the expression of claudin 1 (CLDN1) in MVHP and SSA/P. RESULTS : Gene expression profiling studies conducted between MVHP and SSA/P identified CLDN1 as the most statistically significant differentially expressed gene ( p &lt;0.05). Validation with qRT-PCR confirmed an up-regulation of CLDN1 in BRAF V600E mutant polyps regardless of polyp type ( p &lt;0.0005). Immunohistochemical analysis of CLDN1 expression in BRAF V600E mutant SSA/Ps ( n =53) and MVHPs ( n =111) and BRAF wild-type MVHPs ( n =58), demonstrated a strong correlation between CLDN1 expression and the BRAF V600E mutation in both SSA/P and MVHP samples when compared to wild-type polyps ( p &lt;0.0001). CONCLUSION : This study demonstrates an up regulation of CLDN1 protein in serrated colorectal polyps including MVHP harbouring the BRAF V600E mutation. Our results demonstrated an apparent heterogeneity on the molecular level within the MVHP group and suggest that MVHP with somatic BRAF V600E mutation and up-regulated expression of CLDN1 are closely related to SSA/P and may in fact represent a continuous spectrum of the same neoplastic process within the serrated pathway of colorectal carcinogenesis.</description><subject>Oncology</subject><issn>1936-5233</issn><issn>1944-7124</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>DOA</sourceid><recordid>eNqFUstu1TAUjBCIlsIfIOQfSLAd20k2SCW6pVe6iKo8tpYfx8Uhja_spKJ_j0Ogi266sn00M8eamaJ4S3BFMBHvh2qOagpTRTFhFeYVxt2z4pR0jJUNoez5eq9FyWldnxSvUhowFqSj9GVxQlnHWc3FaeH7US3WTyVBu9_HCCn5MKF9QrsR7tQMFvkJ9WEMEcysRtSryUBEV_m5xBQiOsDKSOhSRR2in27Q_BPQx-vzC_RDYLxDn5dZzRnyunjh1Jjgzb_zrPh-sfvWX5aHL5_2_fmhNJx2c0nb1tmWCMPbrnFW104Loyk0vMXaKbCm44SrRoMATLQiUDfWUuFangfC1GfFftO1QQ3yGP2tivcyKC__DkK8kSrO3owglWkb12EFzAHLSppiAYY44QjVROGsxTYtE0NKEdyDHsFyTUEOcktBrilIzGVOIdPebbTjom_BPpD-254BHzYAZCPuPESZjIfsrPWrz_mn_qkNjwXM6Cdv1PgL7iENYYlTNlkSmajE8uvahLUIhOHcAlbXfwD-FLAO</recordid><startdate>20140801</startdate><enddate>20140801</enddate><creator>Caruso, Maria</creator><creator>Fung, Kim Y.C</creator><creator>Moore, James</creator><creator>Brierley, Gemma V</creator><creator>Cosgrove, Leah J</creator><creator>Thomas, Michelle</creator><creator>Cheetham, Glenice</creator><creator>Brook, Emma</creator><creator>Fraser, Louise M</creator><creator>Tin, Teresa</creator><creator>Tran, Ha</creator><creator>Ruszkiewicz, Andrew</creator><general>Elsevier Inc</general><general>Elsevier</general><scope>6I.</scope><scope>AAFTH</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>DOA</scope></search><sort><creationdate>20140801</creationdate><title>Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation</title><author>Caruso, Maria ; Fung, Kim Y.C ; Moore, James ; Brierley, Gemma V ; Cosgrove, Leah J ; Thomas, Michelle ; Cheetham, Glenice ; Brook, Emma ; Fraser, Louise M ; Tin, Teresa ; Tran, Ha ; Ruszkiewicz, Andrew</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c529t-288fd816c5897fdb3fb6cb2e7580bfaedc9515a7be6e01ba1e37dd26f856e06c3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Oncology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Caruso, Maria</creatorcontrib><creatorcontrib>Fung, Kim Y.C</creatorcontrib><creatorcontrib>Moore, James</creatorcontrib><creatorcontrib>Brierley, Gemma V</creatorcontrib><creatorcontrib>Cosgrove, Leah J</creatorcontrib><creatorcontrib>Thomas, Michelle</creatorcontrib><creatorcontrib>Cheetham, Glenice</creatorcontrib><creatorcontrib>Brook, Emma</creatorcontrib><creatorcontrib>Fraser, Louise M</creatorcontrib><creatorcontrib>Tin, Teresa</creatorcontrib><creatorcontrib>Tran, Ha</creatorcontrib><creatorcontrib>Ruszkiewicz, Andrew</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Directory of Open Access Journals</collection><jtitle>Translational oncology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Caruso, Maria</au><au>Fung, Kim Y.C</au><au>Moore, James</au><au>Brierley, Gemma V</au><au>Cosgrove, Leah J</au><au>Thomas, Michelle</au><au>Cheetham, Glenice</au><au>Brook, Emma</au><au>Fraser, Louise M</au><au>Tin, Teresa</au><au>Tran, Ha</au><au>Ruszkiewicz, Andrew</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation</atitle><jtitle>Translational oncology</jtitle><addtitle>Transl Oncol</addtitle><date>2014-08-01</date><risdate>2014</risdate><volume>7</volume><issue>4</issue><spage>456</spage><epage>463</epage><pages>456-463</pages><issn>1936-5233</issn><eissn>1944-7124</eissn><abstract>Abstract BACKGROUND : Sessile serrated adenomas/polyps (SSA/P) are now recognised precursors of colorectal cancer (CRC) including cancers harbouring somatic BRAF (V600E) mutations. While the morphological diagnostic criteria of SSA/P have been established, distinguishing between small/early SSA/P and microvesicular hyperplastic polyps (MVHP) is challenging and may not be possible in routine practice. METHODS : Gene expression profiling of MVHP ( n =5, all BRAF V600E wild-type ) and SSA/P ( n =5, all BRAF V600E mutant) samples was performed. Quantitative reverse transcription–polymerase chain reaction (qRT-PCR) and immunohistochemical analysis was performed to verify the expression of claudin 1 (CLDN1) in MVHP and SSA/P. RESULTS : Gene expression profiling studies conducted between MVHP and SSA/P identified CLDN1 as the most statistically significant differentially expressed gene ( p &lt;0.05). Validation with qRT-PCR confirmed an up-regulation of CLDN1 in BRAF V600E mutant polyps regardless of polyp type ( p &lt;0.0005). Immunohistochemical analysis of CLDN1 expression in BRAF V600E mutant SSA/Ps ( n =53) and MVHPs ( n =111) and BRAF wild-type MVHPs ( n =58), demonstrated a strong correlation between CLDN1 expression and the BRAF V600E mutation in both SSA/P and MVHP samples when compared to wild-type polyps ( p &lt;0.0001). CONCLUSION : This study demonstrates an up regulation of CLDN1 protein in serrated colorectal polyps including MVHP harbouring the BRAF V600E mutation. Our results demonstrated an apparent heterogeneity on the molecular level within the MVHP group and suggest that MVHP with somatic BRAF V600E mutation and up-regulated expression of CLDN1 are closely related to SSA/P and may in fact represent a continuous spectrum of the same neoplastic process within the serrated pathway of colorectal carcinogenesis.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>24954356</pmid><doi>10.1016/j.tranon.2014.05.009</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record>
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title Claudin-1 Expression Is Elevated in Colorectal Cancer Precursor Lesions Harboring the BRAF V600E Mutation
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