Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial

Abstract Background Expression of human equilibrative nucleoside transporter‐1 (hENT1) is reported to predict survival of gemcitabine (GEM)‐treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. Aim We aimed to i...

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Main Authors: Yukiyasu Okamura, Narikazu Boku, Paula Ghaneh, William Greenhalf, Satoru Yasukawa, Hiroto Narimatsu, Akira Fukutomi, Masaru Konishi, Soichiro Morinaga, Hirochika Toyama, Atsuyuki Maeda, Yasuhiro Shimizu, Shoji Nakamori, Naohiro Sata, Keisuke Yamakita, Amane Takahashi, Wataru Takayama, Ryuzo Yamaguchi, Moriaki Tomikawa, Akio Yanagisawa, John P. Neoptolemos, Katsuhiko Uesaka
Format: Article
Language:English
Published: Wiley 2022-05-01
Series:Cancer Reports
Subjects:
Online Access:https://doi.org/10.1002/cnr2.1507
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author Yukiyasu Okamura
Narikazu Boku
Paula Ghaneh
William Greenhalf
Satoru Yasukawa
Hiroto Narimatsu
Akira Fukutomi
Masaru Konishi
Soichiro Morinaga
Hirochika Toyama
Atsuyuki Maeda
Yasuhiro Shimizu
Shoji Nakamori
Naohiro Sata
Keisuke Yamakita
Amane Takahashi
Wataru Takayama
Ryuzo Yamaguchi
Moriaki Tomikawa
Akio Yanagisawa
John P. Neoptolemos
Katsuhiko Uesaka
author_facet Yukiyasu Okamura
Narikazu Boku
Paula Ghaneh
William Greenhalf
Satoru Yasukawa
Hiroto Narimatsu
Akira Fukutomi
Masaru Konishi
Soichiro Morinaga
Hirochika Toyama
Atsuyuki Maeda
Yasuhiro Shimizu
Shoji Nakamori
Naohiro Sata
Keisuke Yamakita
Amane Takahashi
Wataru Takayama
Ryuzo Yamaguchi
Moriaki Tomikawa
Akio Yanagisawa
John P. Neoptolemos
Katsuhiko Uesaka
author_sort Yukiyasu Okamura
collection DOAJ
description Abstract Background Expression of human equilibrative nucleoside transporter‐1 (hENT1) is reported to predict survival of gemcitabine (GEM)‐treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. Aim We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. Methods The subjects of this study were totally 332 whose formalin‐fixed paraffin‐embedded specimens and/or unstained sections were obtained. The individual H‐scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. Results The highest concordance rate (79.8%) was obtained when the cut‐off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H‐score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p < .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody. Conclusion The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut‐off point and suggests that S‐1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S‐1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.
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spelling doaj.art-15f7769b1eba4cfe9498e1cdf62cb8982022-12-22T02:34:23ZengWileyCancer Reports2573-83482022-05-0155n/an/a10.1002/cnr2.1507Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trialYukiyasu Okamura0Narikazu Boku1Paula Ghaneh2William Greenhalf3Satoru Yasukawa4Hiroto Narimatsu5Akira Fukutomi6Masaru Konishi7Soichiro Morinaga8Hirochika Toyama9Atsuyuki Maeda10Yasuhiro Shimizu11Shoji Nakamori12Naohiro Sata13Keisuke Yamakita14Amane Takahashi15Wataru Takayama16Ryuzo Yamaguchi17Moriaki Tomikawa18Akio Yanagisawa19John P. Neoptolemos20Katsuhiko Uesaka21Division of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Hospital Nagaizumi JapanDivision of Gastrointestinal Medical Oncology National Cancer Center Hospital Tokyo JapanDepartment of Molecular and Clinical Cancer Medicine University of Liverpool Liverpool UKDepartment of Molecular and Clinical Cancer Medicine University of Liverpool Liverpool UKDepartment of Surgical Pathology Kyoto Prefectural University of Medicine Kyoto JapanCancer Prevention and Control Division Kanagawa Cancer Center Yokohama JapanDivision of Gastrointestinal Oncology Shizuoka Cancer Center Shizuoka JapanDivision of Hepato‐Biliary‐Pancreatic Surgery National Cancer Center Hospital East Kashiwa JapanDivision of Gastrointestinal Surgery Kanagawa Cancer Center Yokohama JapanDivision of Hepato‐Biliary‐Pancreatic Surgery Kobe University Kobe JapanDivision of Surgery Ogaki Municipal Hospital Ogaki JapanDivision of Gastrointestinal Surgery Aichi Cancer Center Hospital Nagoya JapanDivision of Surgery National Hospital Organization Osaka National Hospital Osaka JapanDivision of Gastrointestinal Surgery Jichi Medical University Shimotsuke JapanDivision of Metabolism and Biosystemic Science, Department of Medicine Asahikawa Medical University Asahikawa JapanDivision of Gastrointestinal Surgery Saitama Cancer Center Saitama JapanDivision of Gastrointestinal Surgery Chiba Cancer Center Chiba JapanDivision of Surgery Kasugai Municipal Hospital Kasugai JapanDivision of Surgery Tochigi Cancer Center Utsunomiya JapanDepartment of Surgical Pathology Kyoto Prefectural University of Medicine Kyoto JapanDepartment of Molecular and Clinical Cancer Medicine University of Liverpool Liverpool UKDivision of Hepato‐Biliary‐Pancreatic Surgery Shizuoka Cancer Center Hospital Nagaizumi JapanAbstract Background Expression of human equilibrative nucleoside transporter‐1 (hENT1) is reported to predict survival of gemcitabine (GEM)‐treated patients. However, predictive values of immunohistochemical hENT1 expression may differ according to the antibodies, 10D7G2 and SP120. Aim We aimed to investigate the concordance of immunohistochemical hENT1 expression between the two antibodies and prognosis. Methods The subjects of this study were totally 332 whose formalin‐fixed paraffin‐embedded specimens and/or unstained sections were obtained. The individual H‐scores and four classifications according to the staining intensity were applied for the evaluation of hENT1 expression by 10D7G2 and SP120, respectively. Results The highest concordance rate (79.8%) was obtained when the cut‐off between high and low hENT1 expression using SP120 was set between moderate and strong. There were no correlations of hENT1 mRNA level with H‐score (p = .258). Although the hENT1 mRNA level was significantly different among four classifications using SP120 (p = .011), there was no linear relationship among them. Multivariate analyses showed that adjuvant GEM was a significant predictor of the patients with low hENT1 expression using either 10D7G2 (Hazard ratio [HR] 2.39, p = .001) or SP120 (HR 1.84, p < .001). In contrast, agent for adjuvant chemotherapy was not significant predictor for the patients with high hENT1 expression regardless of the kind of antibody. Conclusion The present study suggests that the two antibodies for evaluating hENT1 expression are equivalent depending on the cut‐off point and suggests that S‐1 is the first choice of adjuvant chemotherapy for pancreatic cancer with low hENT1 expression, whereas either S‐1 or GEM can be introduced for the pancreatic cancer with high hENT1 expression, no matter which antibody is used.https://doi.org/10.1002/cnr2.150710D7G2gemcitabinehuman equilibrative nucleoside transporter‐1pancreatic cancerSP120
spellingShingle Yukiyasu Okamura
Narikazu Boku
Paula Ghaneh
William Greenhalf
Satoru Yasukawa
Hiroto Narimatsu
Akira Fukutomi
Masaru Konishi
Soichiro Morinaga
Hirochika Toyama
Atsuyuki Maeda
Yasuhiro Shimizu
Shoji Nakamori
Naohiro Sata
Keisuke Yamakita
Amane Takahashi
Wataru Takayama
Ryuzo Yamaguchi
Moriaki Tomikawa
Akio Yanagisawa
John P. Neoptolemos
Katsuhiko Uesaka
Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial
Cancer Reports
10D7G2
gemcitabine
human equilibrative nucleoside transporter‐1
pancreatic cancer
SP120
title Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial
title_full Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial
title_fullStr Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial
title_full_unstemmed Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial
title_short Concordance of human equilibrative nucleoside transporter‐1 expressions between murine (10D7G2) and rabbit (SP120) antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer: A collaborative study from the JASPAC 01 trial
title_sort concordance of human equilibrative nucleoside transporter 1 expressions between murine 10d7g2 and rabbit sp120 antibodies and association with clinical outcomes of adjuvant chemotherapy for pancreatic cancer a collaborative study from the jaspac 01 trial
topic 10D7G2
gemcitabine
human equilibrative nucleoside transporter‐1
pancreatic cancer
SP120
url https://doi.org/10.1002/cnr2.1507
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