Evaluation of the morphological features and unfavorable prognostic impact of dirty necrosis in renal cell carcinoma

Kuroe, Takashi; Watanabe, Reiko; Kojima, Masaru; Morisue, Ryo; Sugano, Masato; Kuwata, Takeshi; Masuda, Hitoshi; Kusuhara, Shota; Matsubara, Nobuaki; Oda, Shioto; Ushiku, Tetsuo; Ishii, Genichiro

doi:10.1007/s00432-020-03505-2

Cited by 7 publications

(13 citation statements)

References 24 publications

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“…Hematoxylin and eosin (H&E)‐stained slides with the largest necrotic foci were reviewed by the observers, and TN was classified as one of two subtypes: DN and GN. Both DN and GN were defined according to our previous report 6 . First, DN was characterized by abundant neutrophil infiltration and cell detritus.…”

Section: Methodsmentioning

confidence: 99%

“…Both DN and GN were defined according to our previous report. 6 First, DN was characterized by abundant neutrophil infiltration and cell detritus. Second, GN is characterized by eosinophilic ghost cells without features of DN.…”

Section: Methodsmentioning

confidence: 99%

“…In RCC, we previously showed that there were two subtypes of TN: dirty necrosis (DN) and ghost necrosis (GN), 6 which showed different clinicopathological features. DN in RCC is characterized by neutrophil infiltration and cell detritus, providing further unfavorable prognostic information beyond the presence of GN.…”

Section: Introductionmentioning

confidence: 99%

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Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation

et al. 2022

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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.

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Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

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Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation

et al. 2022

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“…Quantitative histological evaluation of whole tumor histological stainings revealed that the degree of necrosis is dependent on the tumor volume, rather than on the presence of BaNPs, as no difference in necrotic areas was found between irradiated tumors and irradiated tumors, which received BaNPs. This correlation was already reported in the literature before and can be explained by the fact that the volume increase of the tumor is faster than the subsequent vascularization 159,160 . The application of RT slowed down or stopped the tumor volume increase and therefore prevented the formation of necrosis.…”

Section: Ex Vivo Analysis Of Banps In Their Local Tumor Environmentsupporting

confidence: 78%

Preclinical evaluation of nanoparticle enhanced breast cancer diagnosis and radiation therapy

Jonas¹

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Triple negative breast cancer (TNBC) is an aggressive type of cancer which makes up 15-20% of all newly diagnosed cases, lacking the main target molecules for tumor specific treatment.Surgery or systemic therapy by chemotherapy are frequently used in the clinic and combined with radiation therapy to improve locoregional control in breast cancer patients after surgery.With a poor prognosis, there is a clear need to explore new treatment options for TNBC. The aim of the here presented PhD project was to evaluate the feasibility to enhance the biological effect of radiation therapy and increase tumor contrast for diagnosis by applying an in vivo microCT imaging system in combination with barium nanoparticles (BaNPs) in a pH8N8 WAP-T-NP8 mouse model for TNBC. Characterization of the BaNPs revealed strong x-ray attenuation and no toxic effects in different cancer and normal cell lines. Furthermore, irradiation of cancer cells using low energy x-rays in the keV range by a microCT resulted in a significant reduction on colony formation capability. In vitro, this low energy irradiation effect on clonogenic tumor cell survival was enhanced in the presence of BaNPs. Next, a subcutaneous lung cancer mouse model in immunodeficient mice and an orthotopic syngeneic mouse model for breast cancer was applied for further in vivo evaluation. Once the treatment plan was optimized regarding the applied x-ray doses and the frequency of irradiation, low energy radiation therapy within a classical in vivo microCT significantly reduced tumor growth or even resulted in shrinkage of the tumors without visible side effects and weight loss in comparison to untreated controls. However, the intratumoral application of BaNPs was not able to increase the irradiation effect on tumor growth kinetics. This might be in part due to inhomogeneous distribution of BaNPs within the tumor observed by microCT imaging. K-edge subtraction imaging as well as x-ray fluorescence of explanted tumor samples confirmed these findings. To localize the BaNPs in 3D to specific sites within the tumor environment and to detect morphological alterations within the tumor due to irradiation in proximity to BaNPs an ex-vivo imaging based analytic platform was established, utilizing co-registration of microCT and histology data. This imaging approach co-localized BaNPs with CD68 positive phagocytic cells and revealed a non-uniform distribution of the BaNPs within the tumor, however with no signs of locally enhanced radiation effects. Furthermore, antibody functionalized BaNPs were generated for systemic application. Analysis of biodistribution revealed that EpCAM labeled BaNPs did not reach the tumor after intra-venous administration, but accumulated in liver and spleen, demonstrated by a strong CT contrast within these organs.

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“…Microscopically observed tumor necrosis is a histopathological feature of the tumor, which is relevant to chronic ischemic injury and angiogenesis [ 10 ] [ 11 ]. Studies on the effects of necrosis on colorectal cancers [ 12 ], cell renal cell carcinomas [ 13 ], and breast cancers [ 14 ] presented that necrosis is a poor prognostic indicator. Recently, tumor necrosis in HCC was found as a poor prognostic factor for patients with HCC who underwent liver resection [ 15 ].…”

Section: Introductionmentioning

confidence: 99%

Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation

Wang

Zhang

et al. 2023

BMC Cancer

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Background Tumor micronecrosis is a histopathological feature predicting poor prognosis in patients with hepatocellular carcinoma (HCC) who underwent liver resection. However, the role of tumor micronecrosis in liver transplantation remains unclear. Methods We retrospectively reviewed patients with HCC who underwent liver transplantation between January 2015 and December 2021 at our center. We then classified them into micronecrosis(−) and micronecrosis(+) groups and compared their recurrence-free survival (RFS) and overall survival (OS). We identified independent prognostic factors using Cox regression analysis and calculated the area under the receiver operating characteristic curve (AUC) to evaluate the predictive value of RFS for patients with HCC after liver transplantation. Results A total of 370 cases with evaluable histological sections were included. Patients of the micronecrosis(+) group had a significantly shorter RFS than those of the micronecrosis(−) group (P = 0.037). Shorter RFS and OS were observed in micronecrosis(+) patients without bridging treatments before liver transplantation (P = 0.002 and P = 0.007), while no differences were detected in those with preoperative antitumor therapies that could cause iatrogenic tumor necrosis. Tumor micronecrosis improved the AUC of Milan criteria (0.77–0.79), the model for end-stage liver disease score (0.70–0.76), and serum alpha-fetoprotein (0.63–0.71) for the prediction of prognosis after liver transplantation. Conclusion Patients with HCC with tumor micronecrosis suffer from a worse prognosis than those without this feature. Tumor micronecrosis can help predict RFS after liver transplantation. Therefore, patients with HCC with tumor micronecrosis should be treated with adjuvant therapy and closely followed after liver transplantation. Clinical trials registration Not Applicable.

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Evaluation of the morphological features and unfavorable prognostic impact of dirty necrosis in renal cell carcinoma

Cited by 7 publications

References 24 publications

Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation

Dirty necrosis in renal cell carcinoma is associated with NETosis and systemic inflammation

Preclinical evaluation of nanoparticle enhanced breast cancer diagnosis and radiation therapy

Tumor micronecrosis predicts poor prognosis of patients with hepatocellular carcinoma after liver transplantation

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