Department of Experimental Clinical Oncology, Aarhus University Hospital, Aarhus, Denmark.
Br J Cancer. 2013 May 28;108(10):2116-22. doi: 10.1038/bjc.2013.167. Epub 2013 Apr 16.
The prognostic impact of tumour-promoting immune cells in cervical cancer is unclear.
Federation of Gynaecology and Obstetrics (FIGO) stage IB and IIA cervical cancer patients (N=101) were assessed for tumour-associated CD66b(+) neutrophils and CD163(+) macrophages by immunohistochemistry in whole tissue sections using stereology. Results were correlated with previous results on tumour-infiltrating CD3(+), CD4(+), and CD8(+) lymphocytes in the same cohort with recurrence-free survival (RFS) as end point.
The highest densities of CD66b(+) neutrophils and CD163(+) macrophages were observed in the peritumoural compartment (median 53.1 cells mm(-2) and 1.3% area fraction, respectively). Above median peritumoural and stromal CD66b(+) neutrophils and peritumoural CD163(+) macrophages were significantly associated with short RFS. Multivariate analysis identified high peritumoural neutrophils (HR 2.27; 95% CI 1.09-4.75; P=0.03), low peritumoural CD8(+) lymphocytes (HR 3.67; 95% CI 1.63-8.25; P=0.002), and lymph node metastases (HR 2.70; 95% CI 1.26-5.76; P=0.01) as independent prognostic factors for short RFS, whereas CD163(+) macrophages were not significant. An index of combined intratumoral and peritumoral CD66b(+) neutrophils to CD8(+) lymphocytes had good discriminatory power for each quartile with 5-year RFS of 92%, 80%, 62%, and 44% (P=0.001).
Tumour-associated neutrophil count is an independent prognostic factor for short RFS in localised cervical cancer. Combining CD66b and CD8 may further improve prognostic stratification. These findings require prospective validation.
肿瘤促进免疫细胞在宫颈癌中的预后影响尚不清楚。
采用组织学立体学方法,对联邦妇产科医师学会(FIGO)分期 IB 和 IIA 期宫颈癌患者(N=101)的肿瘤相关 CD66b(+)中性粒细胞和 CD163(+)巨噬细胞进行评估。结果与同一队列中浸润肿瘤的 CD3(+)、CD4(+)和 CD8(+)淋巴细胞的先前结果相关,以无复发生存(RFS)作为终点。
在肿瘤周围区域观察到最高密度的 CD66b(+)中性粒细胞和 CD163(+)巨噬细胞(中位数分别为 53.1 个细胞/mm(-2)和 1.3%面积分数)。肿瘤周围和基质 CD66b(+)中性粒细胞和肿瘤周围 CD163(+)巨噬细胞高于中位数与 RFS 短有关。多变量分析确定高肿瘤周围中性粒细胞(HR 2.27;95%CI 1.09-4.75;P=0.03)、低肿瘤周围 CD8(+)淋巴细胞(HR 3.67;95%CI 1.63-8.25;P=0.002)和淋巴结转移(HR 2.70;95%CI 1.26-5.76;P=0.01)是 RFS 短的独立预后因素,而 CD163(+)巨噬细胞则不显著。肿瘤内和肿瘤周围 CD66b(+)中性粒细胞与 CD8(+)淋巴细胞的联合指数对每个四分位数的 RFS 具有良好的区分能力,5 年 RFS 分别为 92%、80%、62%和 44%(P=0.001)。
肿瘤相关中性粒细胞计数是局部宫颈癌 RFS 短的独立预后因素。结合 CD66b 和 CD8 可能进一步改善预后分层。这些发现需要前瞻性验证。