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 Le<sup>a/c/x</sup>, sdi-Le<sup>a</sup>, sLe<sup>a</sup>, sLe<sup>x</sup>,...
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2021
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oai:doaj.org-article:f5b3ab7f155943a9889c65a1977579e12021-11-25T17:03:53ZAn Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma10.3390/cancers132257772072-6694https://doaj.org/article/f5b3ab7f155943a9889c65a1977579e12021-11-01T00:00:00Zhttps://www.mdpi.com/2072-6694/13/22/5777https://doaj.org/toc/2072-6694Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Le<sup>a/c/x</sup>, sdi-Le<sup>a</sup>, sLe<sup>a</sup>, sLe<sup>x</sup>, 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<sup>+</sup>) and negative lymph node (LN<sup>−</sup>) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Le<sup>a/c/x</sup>, 94% for sdi-Le<sup>a</sup>, 98% for sLe<sup>a</sup>, 90% for sLe<sup>x</sup>, 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, <i>p</i> < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, <i>p</i> > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN<sup>+</sup>, as well as the distinction of LN<sup>+</sup> from LN<sup>−</sup> tissues. To conclude, this study paves the way for the development and evaluation of Le<sup>a/c/x</sup>-, sdi-Le<sup>a</sup>-, sLe<sup>a</sup>-, sLe<sup>x</sup>- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic.Ruben D. HouvastKira ThijseJesse V. GroenJiaXin ChuaMireille VankemmelbekeLindy G. DurrantJ. Sven D. MieogBert A. BonsingAlexander L. VahrmeijerPeter J. K. KuppenA. Stijn L. P. CrobachCornelis F. M. SierMDPI AGarticlepancreatic canceraberrant glycosylationcarbohydratesmucinsbiomarkersNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENCancers, Vol 13, Iss 5777, p 5777 (2021) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
pancreatic cancer aberrant glycosylation carbohydrates mucins biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 |
| spellingShingle |
pancreatic cancer aberrant glycosylation carbohydrates mucins biomarkers Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Ruben D. Houvast Kira Thijse Jesse V. Groen JiaXin Chua Mireille Vankemmelbeke Lindy G. Durrant J. Sven D. Mieog Bert A. Bonsing Alexander L. Vahrmeijer Peter J. K. Kuppen A. Stijn L. P. Crobach Cornelis F. M. Sier An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
| description |
Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans Le<sup>a/c/x</sup>, sdi-Le<sup>a</sup>, sLe<sup>a</sup>, sLe<sup>x</sup>, 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<sup>+</sup>) and negative lymph node (LN<sup>−</sup>) tissues, and quantified using a semi-automated digital image analysis workflow. Positive expression on PDAC tissues was found on 83% for Le<sup>a/c/x</sup>, 94% for sdi-Le<sup>a</sup>, 98% for sLe<sup>a</sup>, 90% for sLe<sup>x</sup>, 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, <i>p</i> < 0.0001) and healthy pancreatic tissues (MUC1 tumor:pancreas ratio: 1.0, <i>p</i> > 0.9999), respectively. All biomarkers are suitable targets for correct identification of LN<sup>+</sup>, as well as the distinction of LN<sup>+</sup> from LN<sup>−</sup> tissues. To conclude, this study paves the way for the development and evaluation of Le<sup>a/c/x</sup>-, sdi-Le<sup>a</sup>-, sLe<sup>a</sup>-, sLe<sup>x</sup>- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic. |
| format |
article |
| author |
Ruben D. Houvast Kira Thijse Jesse V. Groen JiaXin Chua Mireille Vankemmelbeke Lindy G. Durrant J. Sven D. Mieog Bert A. Bonsing Alexander L. Vahrmeijer Peter J. K. Kuppen A. Stijn L. P. Crobach Cornelis F. M. Sier |
| author_facet |
Ruben D. Houvast Kira Thijse Jesse V. Groen JiaXin Chua Mireille Vankemmelbeke Lindy G. Durrant J. Sven D. Mieog Bert A. Bonsing Alexander L. Vahrmeijer Peter J. K. Kuppen A. Stijn L. P. Crobach Cornelis F. M. Sier |
| author_sort |
Ruben D. Houvast |
| title |
An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
| title_short |
An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
| title_full |
An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
| title_fullStr |
An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
| title_full_unstemmed |
An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma |
| title_sort |
immunohistochemical evaluation of tumor-associated glycans and mucins as targets for molecular imaging of pancreatic ductal adenocarcinoma |
| publisher |
MDPI AG |
| publishDate |
2021 |
| url |
https://doaj.org/article/f5b3ab7f155943a9889c65a1977579e1 |
| work_keys_str_mv |
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