Liver Cancer Institute, Zhong Shan Hospital and Shanghai Medical School, Fudan University, Key Laboratory for Carcinogenesis & Cancer Invasion, The Chinese Ministry of Education, Shanghai, People's Republic of China.
J Hepatol. 2011 Mar;54(3):497-505. doi: 10.1016/j.jhep.2010.07.044. Epub 2010 Oct 1.
BACKGROUND & AIMS: Neutrophil infiltration has been linked to clinical outcome of various cancer types. However, its role in hepatocellular carcinoma (HCC) is unclear. In this study, we investigated prognostic values for intratumoral and peritumoral neutrophils in HCC patients undergoing curative resection.
The expression of CD66b, CD8, TGF-beta, and CD34 was assessed by immunohistochemistry in tissue microarrays containing paired intratumoral and peritumoral tissues from 197 patients receiving curative resection for HCC. Prognostic values for these and other clinicopathologic factors were evaluated.
Intratumoral CD66b(+) neutrophils significantly correlated with CD8(+) T cells (r=0.240, p=0.004), TGF-beta expression (p=0.012), BCLC stage (p=0.016), and early recurrence (p=0.041). Increased intratumoral neutrophils were significantly associated with decreased RFS/OS (p=0.001 and p<0.001, respectively) in univariate analysis and were identified as an independent prognostic factor (HR=1.845, 95% CI=1.169-2.911, p=0.008 for RFS; HR=2.578, 95% CI=1.618-4.106, p<0.001 for OS) in multivariate analysis. Intratumoral neutrophil-to-CD8(+) T cell ratio (iNTR) better predicted the outcome in terms of minimum p values. Intratumoral neutrophils were also demonstrated to be statistically predictive for RFS/OS in the normal AFP subgroup, small HCC subgroup, and validation cohort. However, peritumoral neutrophils were not associated with the outcome of HCC.
The presence of intratumoral neutrophils was a poor prognostic factor for HCC after resection. Intratumoral neutrophil-to-CD8(+) T cell ratio was a better predictor of outcome.
中性粒细胞浸润与多种癌症类型的临床结局相关。然而，其在肝细胞癌（HCC）中的作用尚不清楚。本研究旨在探讨接受根治性切除术的 HCC 患者肿瘤内和肿瘤周围中性粒细胞的预后价值。
采用组织微阵列免疫组织化学法检测 197 例接受 HCC 根治性切除术患者肿瘤内和肿瘤周围配对组织中 CD66b、CD8、TGF-β和 CD34 的表达。评估这些及其他临床病理因素的预后价值。
肿瘤内 CD66b(+)中性粒细胞与 CD8(+)T 细胞（r=0.240，p=0.004）、TGF-β表达（p=0.012）、BCLC 分期（p=0.016）和早期复发（p=0.041）显著相关。肿瘤内中性粒细胞增多与 RFS/OS 降低显著相关（p=0.001 和 p<0.001），在单因素分析中被确定为独立预后因素（RFS 的 HR=1.845，95%CI=1.169-2.911，p=0.008；OS 的 HR=2.578，95%CI=1.618-4.106，p<0.001）。肿瘤内中性粒细胞与 CD8(+)T 细胞比值（iNTR）预测结局的最小 p 值更优。肿瘤内中性粒细胞在 AFP 正常亚组、小 HCC 亚组和验证队列中也被证明对 RFS/OS 具有统计学预测价值。然而，肿瘤周围中性粒细胞与 HCC 患者的预后无关。
肿瘤内中性粒细胞的存在是 HCC 切除后预后不良的因素。肿瘤内中性粒细胞与 CD8(+)T 细胞比值是更好的预后预测指标。
