Abstract 421: The role of the tumor microenvironment of pancreatic cancer to predict treatment outcome
Authors: Steins Anne , Klaassen Remy , Gurney-Champion Oliver , Bijlsma Maarten , Medema Jan Paul , Wijkstra Hessel , van Tienhoven Geertjan , Busch Olivier , Punt Cornelis , Besselink Marc , Wilmink Hanneke , van de Vijver Marc , Stoker Jaap , Nederveen Aart , van Laarhoven Hanneke 
Published: August 2015

Abstract
Introduction: Pancreatic ductal adenocarcinoma (PDAC) ranks 4th on the list of cancer-related deaths which is mostly due to therapy resistance. The tumor microenvironment is one of the main hallmarks to contribute to therapy resistance in which tumors are characterized by large amounts of stroma deposition, and hypovascularization. In this study we assess the use of non-invasive functional magnetic resonance imaging (MRI) for characterization of these tumor microenvironment characteristics and its prognostic and predictive role. Diffusion weighted (DWI) MRI and dynamic contrast enhanced (DCE)-MRI provide insight in stromal content and tumor vascularization. Subsequent correlation of imaging with immunohistochemical (IHC) stainings can validate the biological basis of these imaging modalities. Here, we propose a method to correlate functional MRI to corresponding histology derived tissue characteristics.
Methods: Patients suffering from (borderline) resectable PDAC underwent DWI and DCE-MRI on a 3T Philips scanner prior to resection and/or neoadjuvant chemoradiation. DWI data were fitted with the intra voxel incoherent motion model to obtain, among others, the diffusion coefficient D, while DCE-MRI data were fitted according to the extended Tofts model to retrieve the volume transfer constant Ktrans. After resection, the tissue was sectioned in the axial plane and slices where photographed. One slice with evident tumor was selected for whole mount embedding. Whole mount sections were stained for stromal content (αSMA) and vascular density (CD31) The pancreas contour of the photographed tissue slices was manually outlined. Slices were aligned and stacked to form a 3D volume of the pancreas specimen, which was projected onto the MR images. Stained whole mount sections were aligned with the corresponding tissue photograph and transposed to the MRI accordingly to correlate pathology sections to imaging sections and validate parameters using IHC.
Results: Sixteen patients were included in the study of which four patients have currently been analyzed. Tissue specimens after resection showed good visual agreement with MRI and could be matched using corresponding anatomical landmarks. In addition, Lower D-values, suggesting higher cell density, indeed corresponded with higher stromal content, while higher values on the Ktrans map, suggesting a higher tumor vascularity, corresponded with higher vessel density.
Conclusion: With these preliminary data we demonstrated the feasibility of matching post-operative tissue slices to in vivo MRI of the pancreas. Matching stained whole mount sections to MRI images provides direct information on localization and local tumor heterogeneity for validation of functional MRI parameters. Expanding this work in a larger patient group will provide valuable insights on the underlying biology of functional MRI parameters in pancreatic cancer.
Citation Format: Anne Steins, Remy Klaassen, Oliver Gurney-Champion, Maarten Bijlsma, Jan Paul Medema, Hessel Wijkstra, Geertjan van Tienhoven, Olivier Busch, Cornelis Punt, Marc Besselink, Hanneke Wilmink, Marc van de Vijver, Jaap Stoker, Aart Nederveen, Hanneke van Laarhoven. The role of the tumor microenvironment of pancreatic cancer to predict treatment outcome. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 421. doi:10.1158/1538-7445.AM2015-421