Open AccessDirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation
Author(s) -
Kuroe Takashi,
Watanabe Reiko,
Morisue Ryo,
Miyazaki Saori,
Kojima Motohiro,
Murata Shawhay Charles,
Nakai Tokiko,
Taki Tetsuro,
Sakashita Shingo,
Sakamoto Naoya,
Matsubara Nobuaki,
Masuda Hitoshi,
Ushiku Tetsuo,
Ishii Genichiro
Publication year - 2023
Publication title -
cancer medicine
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 53
ISSN - 2045-7634
DOI - 10.1002/cam4.5249
Subject(s) - necrosis , inflammation , systemic inflammation , tumor necrosis factor alpha , pathology , renal cell carcinoma , neutrophil extracellular traps , apoptosis , medicine , biology , immunology , biochemistry
Aim Dirty necrosis (DN) in renal cell carcinoma (RCC) is morphologically characterized by abundant neutrophil infiltration and has significant potential as an unfavorable prognostic indicator. This study aimed to analyze the pathological and biological features of DN. Materials and Methods A total of 81 RCC tumors, including 33 cases of DN and 48 cases of tumor necrosis without DN features (ghost necrosis [GN]), were enrolled in this study. We compared the number of neutrophils; the activation of cell death pathways, including ferroptosis, NETosis, and apoptosis; the rate of epithelial‐mesenchymal transition (EMT); and proliferation status using immunohistochemistry. We further assessed the effect of the necrosis type on systemic inflammation. Results DN tumors had a significantly higher number of neutrophils in both areas around the necrotic foci and far from the necrotic foci. Ferroptosis status did not differ between DN and GN; however, DN tumors had significantly larger areas exhibiting cell detritus with neutrophil extracellular traps (NETs) detected by citrullinated histone H3 (citH3) than GN tumors. DN tumors also had more apoptotic cells within areas around the necrotic foci. There was no significant difference between the EMT and proliferation status between DN and GN groups. Systemic inflammation markers including C‐reactive protein (CRP), CRP‐to‐albumin ratio (CRP/Alb), platelet‐to‐lymphocyte ratio (PLR), and hemoglobin were significantly higher in patients with DN. In addition, some of these inflammation markers (CRP/Alb and PLR) significantly decreased after surgery. Conclusions DN in RCC is characterized by NETs production and systemic inflammation.