An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma

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

doi:10.3390/cancers13225777

An Immunohistochemical Evaluation of Tumor-Associated Glycans and Mucins as Targets for Molecular Imaging of Pancreatic Ductal Adenocarcinoma

Cancers (Basel). 2021 Nov 18;13(22):5777. doi: 10.3390/cancers13225777.

Authors

Affiliations

¹ Department of Surgery, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
² Scancell Limited, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
³ Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, University Park, Nottingham NG7 2RD, UK.
⁴ Department of Pathology, Leiden University Medical Center, 2333 ZA Leiden, The Netherlands.
⁵ Percuros BV, 2333 CL Leiden, The Netherlands.

Abstract

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 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 Le^a/c/x-, sdi-Le^a-, sLe^a-, sLe^x- and MUC5AC-specific tracers for molecular imaging of PDAC imaging and their subsequent introduction into the clinic.

Keywords: aberrant glycosylation; biomarkers; carbohydrates; mucins; pancreatic cancer.