title: Immunohistochemical analysis of organic anion transporter 2 and reduced folate carrier 1 in colorectal cancer: Significance as a predictor of response to oral uracil/ftorafur plus leucovorin chemotherapy.
abstract: Colorectal cancer is one of the most common malignancies in developed countries and chemotherapy is the standard treatment option for advanced colorectal cancer. Identification of biomarkers for predicting response to uracil/ftorafur plus leucovorin (UFT/LV) chemotherapy is an important issue in colorectal cancer treatment. Organic anion transporter 2 (OAT2) and reduced folate carrier 1 (RFC1) are the major uptake transporters of 5-fluorouracil (5-FU) and LV, respectively. In the present study, the correlation between OAT2 and RFC1 expression and histological response to preoperative UFT-based (UFT or UFT/LV) chemotherapy was investigated. Pre-treatment biopsy specimens obtained from 45 patients were evaluated for OAT2 and RFC1 expression levels by using an immunohistochemical approach. A high expression of OAT2 and RFC1 was significantly correlated with good response to UFT-based chemotherapy (P<0.0001 and P= 0.002, respectively). In multivariate logistic regression analysis, a high OAT2 expression was an independent predictor of good response to UFT-based chemotherapy (P=0.02), unlike RFC1 expression. High expression levels of OAT2 were significantly correlated with a good response in the UFT-treated (P= 0.04) as well as the UFT/LV-treated (P<0.0005) groups; however, RFC1 expression levels were significantly correlated with a good response only in the UFT/LV-treated group (P=0.02). Therefore, immunohistochemical analysis of OAT2 and RFC1 may serve as a useful tool for predicting the efficacy of UFT/LV treatment regimens in colorectal cancer patients.
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142;
authors.forename: Satoshi
authors.initials: S
authors.lastname: Nishino
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142;
authors.forename: Ayumi
authors.initials: A
authors.lastname: Itoh
authors.affiliation: Department of Surgery, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Matsuoka
authors.affiliation: Department of Surgery, School of Medicine, Fujita Health University, Toyoake, Aichi 470-1192, Japan.
authors.forename: Kotaro
authors.initials: K
authors.lastname: Maeda
authors.affiliation: Laboratory of Pathology, Department of Medical Biophysics, Kobe University Graduate School of Health Sciences, Kobe, Hyogo 654-0142;
authors.forename: Shingo
authors.initials: S
authors.lastname: Kamoshida
keywords: colorectal cancer; leucovorin; organic anion transporter 2; reduced folate carrier 1; uracil/ftorafur