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An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma
| Content Provider | MDPI |
|---|---|
| Author | 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. |
| Copyright Year | 2021 |
| Description | Targeted molecular imaging may overcome current challenges in the preoperative and intraoperative delineation of pancreatic ductal adenocarcinoma (PDAC). Tumor-associated glycans $Le^{a/c/x}$, $sdi-Le^{a}$, $sLe^{a}$, $sLe^{x}$, 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 $Le^{a/c/x}$, 94% for $sdi-Le^{a}$, 98% for $sLe^{a}$, 90% for $sLe^{x}$, 88% for sTn, 96% for MUC1 and 67% for M얬, 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 $Le^{a/c/x}$-, $sdi-Le^{a}$-, $sLe^{a}$-, $sLe^{x}$- and M얬-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic. |
| Starting Page | 5777 |
| e-ISSN | 20726694 |
| DOI | 10.3390/cancers13225777 |
| Journal | Cancers |
| Issue Number | 22 |
| Volume Number | 13 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-11-18 |
| Access Restriction | Open |
| Subject Keyword | Cancers Pathology Pancreatic Cancer Aberrant Glycosylation Carbohydrates Mucins Biomarkers |
| Content Type | Text |
| Resource Type | Article |
