肿瘤相关中性粒细胞促进进展期胃癌淋巴结转移的临床病理研究

Clinicopathological study of tumor-associated neutrophils promoting lymph node metastasis in advanced gastric cancer

目的:探讨进展期胃癌(advanced gastric cancer, AGC)患者血液中性粒细胞、癌组织中肿瘤相关中性粒细胞(tumor-associated neutrophils, TANs)和淋巴结转移(lymph node metastasis, LNM)的关系。方法:回顾性分析125例AGC患者外周血中性粒细胞计数、中性粒细胞-淋巴细胞比值(neutrophil-lymphocyte ratio, NLR),以及肿瘤原发灶、癌栓、肿瘤引流淋巴结内TANs的分布,并探讨与LNM的关系;顺序选取39例AGC原发灶进行PD-L1免疫组化检测,探讨TANs与PD-L1表达的相关性。结果:肿瘤浸润深度、组织学低分化、有无脉管侵犯、TANs、NLR与LNM有显著相关性,外周血中性粒细胞计数与LNM无显著相关性。多因素分析显示,有无脉管侵犯(P=0.002)、组织学低分化(P=0.015)和TANs(P=0.003)是LNM的独立危险因素。同时发现原发灶TANs与PD-L1评分呈正相关。脉管内癌栓伴TANs组LNM比例(94.4%)呈现出高于癌栓不伴TANs组(80.5%)的趋势(P=0.094)。中性粒细胞聚集在淋巴结转移阳性组(68.1%)明显高于淋巴结转移阴性组(28.8%)(P=0.000)。结论:本研究从病理形态学方面,说明TANs与胃癌淋巴结转移相关,可能与促进PD-L1相关的免疫抑制微环境相关,值得进一步的机制研究。

Objective:To investigate the relationship between blood neutrophils,tumor-associated neutrophils(TANs)and lymph node metastasis(LNM)in patients with advanced gastric cancer(AGC).Methods:The relationship between the peripheral blood neutrophils count,neutrophil-lymphocyte ratio(NLR),the distribution of TANs in primary lesions,tumor emboli and tumor-draining lymph nodes in 125 patients with AGC and LNM was retrospectively analyzed.Thirty-nine patients with AGC were selected for immunohistochemical detection of PD-L1.The correlation between TANs and PD-L1 expression was investigated.Results:The depth of tumor invasion,poorly histological differentiation,lymphovascular invasion,TANs,NLR were significantly correlated with LNM in 125 patients,while peripheral blood neutrophils count was not significantly correlated with LNM.Multivariate analysis showed that lymphovascular invasion(P=0.002),poorly histological differentiation(P=0.015)and TANs(P=0.003)were independent risk factors for LNM.TANs in primary lesion were positively correlated with PD-L1 score.The proportion of LNM of the lymphatic tumor thrombus with TANs group(94.4%)was higher than that in the group without TANs(80.5%)(P=0.094).The neutrophils aggregation in lymph nodes with tumor metastasis(68.1%)was significantly higher than that in those without tumor metastasis(28.8%)(P=0.000).Conclusion:Based on histopathological morphology,this study indicates that TANs are related with the LNM in gastric cancer,and may be related to the immunosuppressive microenvironment of PD-L1,which is worthy of further study on its mechanism.