Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-02-01
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| Series: | Cancer Medicine |
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| Online Access: | https://doi.org/10.1002/cam4.5249 |
| _version_ | 1828002780994863104 |
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| author | Takashi Kuroe Reiko Watanabe Ryo Morisue Saori Miyazaki Motohiro Kojima Shawhay Charles Murata Tokiko Nakai Tetsuro Taki Shingo Sakashita Naoya Sakamoto Nobuaki Matsubara Hitoshi Masuda Tetsuo Ushiku Genichiro Ishii |
| author_facet | Takashi Kuroe Reiko Watanabe Ryo Morisue Saori Miyazaki Motohiro Kojima Shawhay Charles Murata Tokiko Nakai Tetsuro Taki Shingo Sakashita Naoya Sakamoto Nobuaki Matsubara Hitoshi Masuda Tetsuo Ushiku Genichiro Ishii |
| author_sort | Takashi Kuroe |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-10T06:49:07Z |
| format | Article |
| id | doaj.art-14b24518d33246a0b19a10ed9aa5ebf2 |
| institution | Directory Open Access Journal |
| issn | 2045-7634 |
| language | English |
| last_indexed | 2024-04-10T06:49:07Z |
| publishDate | 2023-02-01 |
| publisher | Wiley |
| record_format | Article |
| series | Cancer Medicine |
| spelling | doaj.art-14b24518d33246a0b19a10ed9aa5ebf22023-02-28T08:51:57ZengWileyCancer Medicine2045-76342023-02-011244557456710.1002/cam4.5249Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammationTakashi Kuroe0Reiko Watanabe1Ryo Morisue2Saori Miyazaki3Motohiro Kojima4Shawhay Charles Murata5Tokiko Nakai6Tetsuro Taki7Shingo Sakashita8Naoya Sakamoto9Nobuaki Matsubara10Hitoshi Masuda11Tetsuo Ushiku12Genichiro Ishii13Department of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDivision of Pathology, Exploratory Oncology Research and Clinical Trial Center National Cancer Center Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Medical Oncology National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Urology National Cancer Center Hospital East Kashiwa Chiba JapanDepartment of Pathology, Graduate School of Medicine The University of Tokyo Tokyo JapanDepartment of Pathology and Clinical Laboratories National Cancer Center Hospital East Kashiwa Chiba JapanAbstract 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.https://doi.org/10.1002/cam4.5249dirty necrosisNETosisneutrophil extracellular trapssystemic inflammationtumor necrosis |
| spellingShingle | Takashi Kuroe Reiko Watanabe Ryo Morisue Saori Miyazaki Motohiro Kojima Shawhay Charles Murata Tokiko Nakai Tetsuro Taki Shingo Sakashita Naoya Sakamoto Nobuaki Matsubara Hitoshi Masuda Tetsuo Ushiku Genichiro Ishii Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation Cancer Medicine dirty necrosis NETosis neutrophil extracellular traps systemic inflammation tumor necrosis |
| title | Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation |
| title_full | Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation |
| title_fullStr | Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation |
| title_full_unstemmed | Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation |
| title_short | Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation |
| title_sort | dirty necrosis in renal cell carcinoma is associated with netosis and systemic inflammation |
| topic | dirty necrosis NETosis neutrophil extracellular traps systemic inflammation tumor necrosis |
| url | https://doi.org/10.1002/cam4.5249 |
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