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

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.

Prognostic impact of the number of peri-tumoral alveolar macrophages in patients with stage I lung adenocarcinoma.

PURPOSE: Intratumoral macrophages are reportedly involved in tumor progression in non-small cell lung cancer; however, little is known about the prognostic impact and function of alveolar macrophages (AMs). This study aims to investigate the prognostic impact of the number of peri-tumoral AMs in patients with stage I lung adenocarcinoma. METHODS: We investigated 514 patients with pathological stage I lung adenocarcinoma who underwent complete resection with lobectomy or pneumonectomy. The numbers of peri-tumoral AMs were counted, and patients were classified into two groups based on the number of peri-tumoral AMs. Using the Cancer Genome Atlas (TCGA) database of stage I lung adenocarcinoma, we compared gene expression profiles of high and low peri-tumoral AM contents. RESULTS: The median number of peri-tumoral AMs per alveolar space was 15.5. Patients with a high peri-tumoral AM content had significantly shorter disease-free survival and overall survival than patients with a low peri-tumoral AM content (both p < 0.01). In the multivariate analyses, a higher number of peri-tumoral AMs were an independent prognostic factor (p = 0.02). The analysis of TCGA database revealed that patients with a high peri-tumoral AM content had shorter disease-free survival than those with a low peri-tumoral AM content (p = 0.04). Gene expression analysis of TCGA stage I lung adenocarcinoma revealed enrichment of biological processes, such as chemotaxis and epithelial proliferation, in patients with a high peri-tumoral AM content. CONCLUSION: The number of peri-tumoral AMs had a strong impact on disease-free survival in patients with stage I lung adenocarcinoma.