An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma
Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Lea/c/x, sdi-Lea, sLea, sLex, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as tar...
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| Veröffentlicht in: | Cancers 2021-11, Vol.13 (22), p.5777 |
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| creator | Houvast, Ruben D. Thijse, Kira Groen, Jesse V. Chua, JiaXin Vankemmelbeke, Mireille Durrant, Lindy G. Mieog, J. Sven D. Bonsing, Bert A. Vahrmeijer, Alexander L. Kuppen, Peter J. K. Crobach, A. Stijn L. P. Sier, Cornelis F. M. |
| description | Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Lea/c/x, sdi-Lea, sLea, sLex, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as targets for PDAC imaging. To evaluate their PDAC molecular imaging potential, biomarker expression was determined using immunohistochemistry on PDAC, (surrounding) chronic pancreatitis (CP), healthy pancreatic, duodenum, positive (LN+) and negative lymph node (LN−) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Lea/c/x, 94% for sdi-Lea, 98% for sLea, 90% for sLex, 88% for sTn, 96% for MUC1 and 67% for MUC5AC, where all were not affected by the application of neoadjuvant therapy. Compared to PDAC, all biomarkers were significantly lower expressed on CP, healthy pancreatic and duodenal tissues, except for sTn and MUC1, which showed a strong expression on duodenum (sTn tumor:duodenum ratio: 0.6, p < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, p > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN+, as well as the distinction of LN+ from LN− tissues. To conclude, this study paves the way for the development and evaluation of Lea/c/x-, sdi-Lea-, sLea-, sLex- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic. |
| doi_str_mv | 10.3390/cancers13225777 |
| format | Article |
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Sven D. ; Bonsing, Bert A. ; Vahrmeijer, Alexander L. ; Kuppen, Peter J. K. ; Crobach, A. Stijn L. P. ; Sier, Cornelis F. M.</creator><creatorcontrib>Houvast, Ruben D. ; Thijse, Kira ; Groen, Jesse V. ; Chua, JiaXin ; Vankemmelbeke, Mireille ; Durrant, Lindy G. ; Mieog, J. Sven D. ; Bonsing, Bert A. ; Vahrmeijer, Alexander L. ; Kuppen, Peter J. K. ; Crobach, A. Stijn L. P. ; Sier, Cornelis F. M.</creatorcontrib><description>Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Lea/c/x, sdi-Lea, sLea, sLex, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as targets for PDAC imaging. To evaluate their PDAC molecular imaging potential, biomarker expression was determined using immunohistochemistry on PDAC, (surrounding) chronic pancreatitis (CP), healthy pancreatic, duodenum, positive (LN+) and negative lymph node (LN−) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Lea/c/x, 94% for sdi-Lea, 98% for sLea, 90% for sLex, 88% for sTn, 96% for MUC1 and 67% for MUC5AC, where all were not affected by the application of neoadjuvant therapy. Compared to PDAC, all biomarkers were significantly lower expressed on CP, healthy pancreatic and duodenal tissues, except for sTn and MUC1, which showed a strong expression on duodenum (sTn tumor:duodenum ratio: 0.6, p < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, p > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN+, as well as the distinction of LN+ from LN− tissues. To conclude, this study paves the way for the development and evaluation of Lea/c/x-, sdi-Lea-, sLea-, sLex- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic.</description><identifier>ISSN: 2072-6694</identifier><identifier>EISSN: 2072-6694</identifier><identifier>DOI: 10.3390/cancers13225777</identifier><identifier>PMID: 34830932</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Adenocarcinoma ; Automation ; Biobanks ; Biomarkers ; Disease ; Duodenum ; Image processing ; Immunohistochemistry ; Lymph nodes ; Lymphatic system ; Metastases ; Metastasis ; Mucin ; Pancreatic cancer ; Pancreatitis ; Patients ; Polysaccharides ; Proteins ; Small intestine ; Statistical analysis ; Surgery ; Tracers ; Tumor cells</subject><ispartof>Cancers, 2021-11, Vol.13 (22), p.5777</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c398t-3fb9540e221e2c00ce1b9d663159ad5a02540b34f4c2a0af9b9cc641809020e83</citedby><cites>FETCH-LOGICAL-c398t-3fb9540e221e2c00ce1b9d663159ad5a02540b34f4c2a0af9b9cc641809020e83</cites><orcidid>0000-0002-4337-2758 ; 0000-0003-4513-5737 ; 0000-0002-8813-0330 ; 0000-0002-2438-4665 ; 0000-0002-0294-3251</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616289/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC8616289/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,881,27903,27904,53769,53771</link.rule.ids></links><search><creatorcontrib>Houvast, Ruben D.</creatorcontrib><creatorcontrib>Thijse, Kira</creatorcontrib><creatorcontrib>Groen, Jesse V.</creatorcontrib><creatorcontrib>Chua, JiaXin</creatorcontrib><creatorcontrib>Vankemmelbeke, Mireille</creatorcontrib><creatorcontrib>Durrant, Lindy G.</creatorcontrib><creatorcontrib>Mieog, J. Sven D.</creatorcontrib><creatorcontrib>Bonsing, Bert A.</creatorcontrib><creatorcontrib>Vahrmeijer, Alexander L.</creatorcontrib><creatorcontrib>Kuppen, Peter J. K.</creatorcontrib><creatorcontrib>Crobach, A. Stijn L. P.</creatorcontrib><creatorcontrib>Sier, Cornelis F. M.</creatorcontrib><title>An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma</title><title>Cancers</title><description>Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Lea/c/x, sdi-Lea, sLea, sLex, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as targets for PDAC imaging. To evaluate their PDAC molecular imaging potential, biomarker expression was determined using immunohistochemistry on PDAC, (surrounding) chronic pancreatitis (CP), healthy pancreatic, duodenum, positive (LN+) and negative lymph node (LN−) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Lea/c/x, 94% for sdi-Lea, 98% for sLea, 90% for sLex, 88% for sTn, 96% for MUC1 and 67% for MUC5AC, where all were not affected by the application of neoadjuvant therapy. Compared to PDAC, all biomarkers were significantly lower expressed on CP, healthy pancreatic and duodenal tissues, except for sTn and MUC1, which showed a strong expression on duodenum (sTn tumor:duodenum ratio: 0.6, p < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, p > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN+, as well as the distinction of LN+ from LN− tissues. 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Sven D.</au><au>Bonsing, Bert A.</au><au>Vahrmeijer, Alexander L.</au><au>Kuppen, Peter J. K.</au><au>Crobach, A. Stijn L. P.</au><au>Sier, Cornelis F. M.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma</atitle><jtitle>Cancers</jtitle><date>2021-11-18</date><risdate>2021</risdate><volume>13</volume><issue>22</issue><spage>5777</spage><pages>5777-</pages><issn>2072-6694</issn><eissn>2072-6694</eissn><abstract>Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Lea/c/x, sdi-Lea, sLea, sLex, sTn as well as mucin-1 (MUC1) and mucin-5AC (MU5AC) have gained significant interest as targets for PDAC imaging. To evaluate their PDAC molecular imaging potential, biomarker expression was determined using immunohistochemistry on PDAC, (surrounding) chronic pancreatitis (CP), healthy pancreatic, duodenum, positive (LN+) and negative lymph node (LN−) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Lea/c/x, 94% for sdi-Lea, 98% for sLea, 90% for sLex, 88% for sTn, 96% for MUC1 and 67% for MUC5AC, where all were not affected by the application of neoadjuvant therapy. Compared to PDAC, all biomarkers were significantly lower expressed on CP, healthy pancreatic and duodenal tissues, except for sTn and MUC1, which showed a strong expression on duodenum (sTn tumor:duodenum ratio: 0.6, p < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, p > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN+, as well as the distinction of LN+ from LN− tissues. 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| subjects | Adenocarcinoma Automation Biobanks Biomarkers Disease Duodenum Image processing Immunohistochemistry Lymph nodes Lymphatic system Metastases Metastasis Mucin Pancreatic cancer Pancreatitis Patients Polysaccharides Proteins Small intestine Statistical analysis Surgery Tracers Tumor cells |
| title | An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
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