Research ArticlesAbundance of the Organic Anion-transporting Polypeptide OATP4A1 in Early-Stage Colorectal Cancer Patients: Association With Disease RelapseBuxhofer-Ausch, Veronika MD*,†; Sheikh, Maidah MSc‡; Ausch, Christoph MD†; Zotter, Simone MSc‡; Bauer, Heike MD§; Mollik, Marina BMA∥; Reiner, Angelika MD∥; Gleiss, Andreas PhD¶; Jäger, Walter PhD#; Sebesta, Christian MD**; Kriwanek, Stephan MD§; Thalhammer, Theresia PhD‡Author Information *Department of Internal Medicine 1, Elisabethinen Hospital Linz, Fadingerstrasse 1, Linz †Tumorzentrum Gespag-Elisabethinen, Landeskrankenhaus Steyr, Steyr ‡Department of Pathophysiology and Allergy Research, Medical University of Vienna Departments of §Surgery ∥Pathology **Internal Medicine II, Donauspital ¶Center for Medical Statistics, Informatics, and Intelligent Systems, Medical University of Vienna #Department of Clinical Pharmacology, University of Vienna, Vienna, Austria V.B.-A.: collected data, performed research, and wrote the manuscript. C.A. and H.B.: collected data. M.S., S.Z., and A.R.: performed the immunohistochemical analysis and data interpretation. A.G.: conducted the statistical analysis. M.M. and A.R.: performed the pathologic analyses. C.S. and S.K.: supervised the research project. W.J.: revised the manuscript. T.T.: designed and supervised the research project and wrote the manuscript. Supported by the Medical Fund of the Mayor of Vienna, P1004. The authors declare no conflict of interest. Reprints: Veronika Buxhofer-Ausch, MD, Department of Internal Medicine 1, Krankenhaus Elisabethinen Linz Fadingerstrasse 1, 4020 Linz, Austria (e-mail: [email protected]). Applied Immunohistochemistry & Molecular Morphology: March 2019 - Volume 27 - Issue 3 - p 185-194 doi: 10.1097/PAI.0000000000000557 Buy SDC Metrics Abstract The abundance of OATP4A1 in colorectal cancer (CRC) might be related to tumor progression. This was studied by immunohistochemistry on paraffin-embedded samples obtained from 178 patients (43 patients with a relapse within 5 y) with early-stage CRC. Positivity for OATP4A1 in tumor cells and noncancerous mucosal cells was proved by double-immunofluorescence staining with antibodies against OATP4A1 and keratin 8, whereas antibodies against appropriate CD markers were used to identify immune cells. Automated microscopic image analysis was used to measure the percentage of OATP4A1-positive cells and OATP4A1 staining intensity in tumor, immune, and adjacent normal-looking mucosal cells separately, as well as in the mucosal and immune cells of 14 nonmalignant tissue samples. In CRC the percentage of OATP4A1-positive cells, but not staining intensity, was significantly higher in tumor and mucosal cells adjacent to the tumor compared to the mucosa of nonmalignant samples (P<0.001 each). No difference was registered between immune cells in malignant and nonmalignant samples. Importantly, high levels of OATP4A1 in immune (odds ratio, 0.73; confidence interval, 0.63-0.85; P<0.001), and tumor cells (odds ratio, 0.79; confidence interval, 0.69-0.91; P<0.001) are significantly associated with a low risk of recurrence and also significantly enhance the discriminative power of other clinical parameters [such as International Union Against Cancer (UICC), adjuvant therapy, localization of the primary tumor] of the risk of relapse (receiver operating characteristics analysis; P=0.002). Using an advanced digital microscopic quantification procedure, we showed that OATP4A1 abundance is negatively associated with tumor recurrence in early-stage CRC. This digital scoring procedure may serve as a novel tool for the assessment of potential prognostic markers in early-stage CRC. Copyright © 2018 Wolters Kluwer Health, Inc. All rights reserved.