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Annals of Surgical Oncology
Published in: Annals of Surgical Oncology 3/2024

05-12-2023 | Cholangiocarcinoma | Translational Research

Impact of Neutrophil Extracellular Traps Identified by Citrullinated Histone H3 Immunohistochemistry for Postoperative Prognosis in Patients with Extrahepatic Cholangiocarcinomas

Authors: Hiroyuki Yamamoto, MD, Yoshitsugu Nakanishi, MD, PhD, Tomoko Mitsuhashi, MD, PhD, Yutaka Hatanaka, PhD, Kanako Hatanaka, PhD, Ayae Nange, MS, Yusuke Yoshida, MD, Norito Ino, MD, Masaru Go, MD, Keisuke Okamura, MD, PhD, Takahiro Tsuchikawa, MD, PhD, Toru Nakamura, MD, PhD, Takehiro Noji, MD, PhD, Toshimichi Asano, MD, PhD, Aya Matsui, MD, PhD, Kimitaka Tanaka, MD, PhD, Soichi Murakami, MD, PhD, Yuma Ebihara, MD, PhD, Yo Kurashima, MD, PhD, Toshiaki Shichinohe, MD, PhD, Satoshi Hirano, MD, PhD

Published in: Annals of Surgical Oncology | Issue 3/2024

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Abstract

Background

Neutrophil extracellular traps (NETs) are extracellular chromatin structures composed of cytoplasmic, granular, and nuclear components of neutrophils. Recently, NETs have received much attention for their role in tumor biology; however, their impact on the postoperative prognosis of patients with extrahepatic cholangiocarcinomas (EHCCs) remains unclear. The purpose of this study was to clarify the impact of NETs identified by immunohistochemical citrullinated histone H3 (Cit-H3) staining on postoperative overall survival (OS) in patients with perihilar cholangiocarcinoma (PHCC) and distal cholangiocarcinoma (DCC).

Methods

This study included 318 patients with EHCC (PHCC, n = 192; DCC, n = 126) who underwent surgical resection with curative intent. Neutrophils and NETs were identified by immunohistochemistry using antibodies against CD15 and Cit-H3, respectively. Based on the distribution of CD15 and Cit-H3 expression in the tumor bed, the patients were classified into four groups: one negative group and three subgroups of the positive group (diffuse, intermediate, and focal subgroups).

Results

No significant difference was found in the postoperative OS rate depending on the distribution of CD15 expression in patients with PHCC or DCC. However, the three subgroups with positive Cit-H3 expression had significantly poorer OS than the negative group for both PHCC and DCC. Moreover, positive Cit-H3 was an independent OS factor in the multivariable analyses of PHCC (hazard ratio [HR] 1.69, 95% confidence interval [CI] 1.11–2.59, P = 0.0115) and DCC (HR 2.03; 95% CI 1.21–3.42, P = 0.0057).

Conclusions

The presence of NETs in the tumor microenvironment may have adverse prognostic effects in patients with EHCCs.
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Metadata
Title
Impact of Neutrophil Extracellular Traps Identified by Citrullinated Histone H3 Immunohistochemistry for Postoperative Prognosis in Patients with Extrahepatic Cholangiocarcinomas
Authors
Hiroyuki Yamamoto, MD
Yoshitsugu Nakanishi, MD, PhD
Tomoko Mitsuhashi, MD, PhD
Yutaka Hatanaka, PhD
Kanako Hatanaka, PhD
Ayae Nange, MS
Yusuke Yoshida, MD
Norito Ino, MD
Masaru Go, MD
Keisuke Okamura, MD, PhD
Takahiro Tsuchikawa, MD, PhD
Toru Nakamura, MD, PhD
Takehiro Noji, MD, PhD
Toshimichi Asano, MD, PhD
Aya Matsui, MD, PhD
Kimitaka Tanaka, MD, PhD
Soichi Murakami, MD, PhD
Yuma Ebihara, MD, PhD
Yo Kurashima, MD, PhD
Toshiaki Shichinohe, MD, PhD
Satoshi Hirano, MD, PhD
Publication date
05-12-2023
Publisher
Springer International Publishing
Published in
Annals of Surgical Oncology / Issue 3/2024
Print ISSN: 1068-9265
Electronic ISSN: 1534-4681
DOI
https://doi.org/10.1245/s10434-023-14638-2

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