Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery

Abstract

PurposeThe purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma.ProceduresThe expression of eight potential imaging targets was assessed by the target selection criteria (TASC)—score and immunohistochemical analysis in normal pancreatic tissue (n = 9), pancreatic (n = 137), and periampullary (n = 28) adenocarcinoma.ResultsIntegrin αvβ6, carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p < 0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients.ConclusionsThe results of this study show that integrin αvβ6, CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

Development and Preclinical Validation of a Cysteine Knottin Peptide Targeting Integrin αvβ6 for Near-infrared Fluorescent-guided Surgery in Pancreatic Cancer

“…Integrin avb6 has been shown to be a promising target for identification of PDAC, and differentiation with pancreatitis and normal pancreatic tissue, with retained expression in vital tumor cells after neoadjuvant therapy (12)(13)(14)(15)30). Nowadays, the majority of patients will receive neoadjuvant therapy prior to surgery due to late onset of symptoms and therefore, presentation with locally advanced disease, or borderline resectable tumors.…”

“…In previous studies, out of a panel of different biomarkers, we selected integrin avb6 as the most promising target for pancreatic cancer detection, based on its potential to discriminate tumor and inflammation, to identify lymph node metastases, and to differentiate between viable tumor cells and necrosis in patients who received neoadjuvant therapy (12,13).…”

Fluorescent‐guided surgery for sentinel lymph node detection in gastric cancer and carcinoembryonic antigen targeted fluorescent‐guided surgery in colorectal and pancreatic cancer

“…In search of other tumor‐specific imaging targets, de Geus et al found that CEA, integrin αvβ6, epithelial growth factor receptor and urokinase plasminogen activator receptor seem suitable targets for pancreatic imaging . In this study, 158 of 165 (96%) of pancreatic and periampullary adenocarcinomas could be identified using CEA immunohistochemistry.…”

Correlation Between Preoperative Serum Carcinoembryonic Antigen Levels and Expression on Pancreatic and Rectal Cancer Tissue

“…In this study, only 6 of 20 tissues showed homogeneous CEA expression and 15 of 20 tissues showed expression in >50% of neoplastic pancreatic cells. Previous studies reported CEA expression in approximately 60% to 75% of PDAC tissues 3,18. Serum CEA measurements were performed using the Elecsys CEA assay (Roche Diagnostics), which is previously described to be specific for CEACAM5 as well as for NCA-2, the nonspecific cross reacting antigen-2 19.…”