High levels of tumor-associated neutrophils are associated with improved overall survival in patients with stage II colorectal cancer
High levels of tumor-associated neutrophils are associated with improved overall survival in patients with stage II colorectal cancer
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DOI：
10.1371/journal.pone.0188799
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发表时间：
2017-12-06
期刊：
影响因子：
3.7
通讯作者：
Hanson, Joshua A.
中科院分区：
文献类型：
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作者：
Berry, Ryan S.;Xiong, Meng-Jun;Hanson, Joshua A.
关于高肿瘤相关中性粒细胞 (TAN) 是否与结直肠癌 (CRC) 结局相关，存在相互矛盾的报道。之前的研究人员使用非中性粒细胞特异性免疫组织化学 (IHC) 染色来计算 TAN。我们检查了通过多区域手动计数确定的 TAN 水平是否可以预测预后。获得了 IRB 的批准，两名对阶段/结果不知情的病理学家在每个样本 20 个高倍视野 (HPF) 中计算了 TAN。 TAN 分数定义为这些计数的平均值。高 TAN 被定义为等于或高于该阶段的中位分数。从记录中获取人口统计学、肿瘤特征和总生存期 (OS)，并检查其与 TAN 评分的关联。在一部分样品中进行精氨酸酶表达的 IHC。共纳入 221 名患者。与低 TAN 评分的 II 期患者相比，高 TAN 评分的 II 期患者的 OS 为 232 个月（OS = 85 个月，p = 0.03）。在控制年龄和性别的多变量分析（HR 0.48，CI 0.25-0.91，p = 0.026）中，生存获益持续存在。与男性相比，女性的生存率更高，尽管只有 12 名 IV 期患者，但 III/IV 期患者的 TAN 计数与预后没有显着相关性。精氨酸酶染色没有提供额外的信息。高 TAN 的 II 期结直肠癌患者的寿命比低 TAN 患者的寿命长近 3 倍。患有 II 期疾病和高 TAN 计数的女性似乎推动了 II 期患者的生存获益，并且所有阶段的总生存率均有所提高。
Conflicting reports regarding whether high tumor-associated neutrophils (TAN) are associated with outcomes in colorectal cancer (CRC) exist. Previous investigators have counted TAN using non-neutrophil-specific immunohistochemistry (IHC) stains. We examined whether TAN levels as determined by multi-field manual counting would predict prognosis. IRB approval was obtained and two pathologists, blinded to stage/outcome, counted TAN in 20 high power fields (HPF) per specimen. TAN score was defined as the mean of these counts. High TAN was defined as at or greater than the median score for that stage. Demographics, tumor characteristics, and overall survival (OS) were obtained from the records and examined for association with TAN score. IHC for arginase expression was performed in a subset of samples. 221 patients were included. Stage II patients with high TAN scores had an OS of 232 months as compared to those with low TAN (OS = 85 months, p = 0.03). The survival benefit persisted in multivariable analysis (HR 0.48, CI 0.25-0.91, p = 0.026) controlling for age and sex. Women had increased survival as compared to men, and there were no significant prognostic associations with TAN count in stage III/IV patients, although there were only 12 stage IV patients. Arginase staining did not provide additional information. Stage II colorectal cancer patients with high TAN live nearly 3 times longer than those with low TAN. Women with stage II disease and high TAN counts appear to be driving the survival benefit seen in the stage II patients and have increased overall survival in all stages.