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 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.

• 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
• Journal: Cancer reports (Hoboken, N.J.) (Cancer Rep (Hoboken)) Vol. 5 Issue 5 Pg. e1507 (05 2022) ISSN: 2573-8348 [Electronic] United States
• PMID: 34327872 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Cancer Reports published by Wiley Periodicals LLC.

Chemical References

• Antimetabolites, Antineoplastic
• Equilibrative Nucleoside Transporter 1
• RNA, Messenger

Topics

• Animals
• Antimetabolites, Antineoplastic (therapeutic use)
• Chemotherapy, Adjuvant
• Equilibrative Nucleoside Transporter 1 (analysis, genetics)
• Humans
• Mice
• Pancreatic Neoplasms (drug therapy)
• RNA, Messenger (therapeutic use)
• Rabbits