Oi Hajime, Taki Tetsuro, Kuroe Takashi, Sakamoto Naoya, Sakashita Shingo, Kojima Motohiro, Sugiyama Eri, Umemura Shigeki, Sakai Tetsuya, Izumi Hiroki, Zenke Yoshitaka, Matsumoto Shingo, Yoh Kiyotaka, Ishii Makoto, Tsuboi Masahiro, Goto Koichi, Ishii Genichiro
Department of Pathology and Clinical Laboratories, National Cancer Center Hospital East, Kashiwa, Japan.
Department of Thoracic Oncology, National Cancer Center Hospital East, Kashiwa, Japan.
Cancer Sci. 2025 Feb;116(2):524-532. doi: 10.1111/cas.16332. Epub 2024 Nov 18.
Pulmonary pleomorphic carcinoma (PC) is a rare non-small-cell lung carcinoma (NSCLC) with a poor prognosis, characterized by tumor necrosis (TN). NETosis is a form of neutrophil-specific cell death, which is morphologically characterized by prominent neutrophil infiltration and cell detritus in the necrotic foci. Seventy-six patients with pulmonary PC who underwent complete resection were enrolled. Tumor necrosis was evaluated using digitally scanned resected specimens. The regions of NETosis were quantified using citrullinated histone H3 (citH3)- and myeloperoxidase-positive regions. We examined the association between the NETosis area and the prognostic outcomes and assessed the correlation between the NETosis area and systemic inflammation. Tumor necrosis was observed in 70 patients (92%). In all the cases, the TN region was accompanied by a citH3-positive region. The patients with high NETosis area (n = 54) had significantly shorter overall survival than those with low NETosis area (n = 16) (p = 0.013). Furthermore, a high NETosis area was an independent poor prognostic factor in the multivariate analyses. Systemic inflammatory markers, including C-reactive protein (CRP), CRP-to-albumin ratio, and neutrophil-to-lymphocyte ratio, were significantly higher in patients with high NETosis area than in those with low NETosis area. Furthermore, the levels of these inflammatory markers were significantly decreased postsurgery. This study shows that in surgically resected pulmonary PC, patients with high NETosis areas have higher systemic inflammation and worse prognosis.
肺多形性癌（PC）是一种罕见的非小细胞肺癌（NSCLC），预后较差，其特征为肿瘤坏死（TN）。NETosis是中性粒细胞特异性细胞死亡的一种形式，其形态学特征是坏死灶中有明显的中性粒细胞浸润和细胞碎屑。纳入76例行根治性切除术的肺PC患者。使用数字扫描的切除标本评估肿瘤坏死情况。使用瓜氨酸化组蛋白H3（citH3）和髓过氧化物酶阳性区域对NETosis区域进行定量。我们研究了NETosis面积与预后结果之间的关联，并评估了NETosis面积与全身炎症之间的相关性。70例患者（92%）观察到肿瘤坏死。在所有病例中，TN区域均伴有citH3阳性区域。NETosis面积高的患者（n = 54）的总生存期明显短于NETosis面积低的患者（n = 16）（p = 0.013）。此外，在多变量分析中，NETosis面积高是一个独立的不良预后因素。全身炎症标志物，包括C反应蛋白（CRP）、CRP与白蛋白比值和中性粒细胞与淋巴细胞比值，NETosis面积高的患者明显高于NETosis面积低的患者。此外，这些炎症标志物的水平在术后明显降低。本研究表明，在手术切除的肺PC中，NETosis面积高的患者全身炎症更严重，预后更差。
