Erschienen in:
05.12.2023 | Translational Research
Impact of Neutrophil Extracellular Traps Identified by Citrullinated Histone H3 Immunohistochemistry for Postoperative Prognosis in Patients with Extrahepatic Cholangiocarcinomas
verfasst von:
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
Erschienen in:
Annals of Surgical Oncology
|
Ausgabe 3/2024
Einloggen, um Zugang zu erhalten
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.