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原发性可手术乳腺癌患者全身炎症反应、肿瘤增殖活性、T淋巴细胞和巨噬细胞浸润、微血管密度与生存之间的关系

The relationship between the systemic inflammatory response, tumour proliferative activity, T-lymphocytic and macrophage infiltration, microvessel density and survival in patients with primary operable breast cancer.

作者信息

Murri A M Al, Hilmy M, Bell J, Wilson C, McNicol A-M, Lannigan A, Doughty J C, McMillan D C

机构信息

University Department of Surgery, University of Glasgow - Faculty of Medicine, Royal and Western Infirmaries, Glasgow G31 2ER, UK.

出版信息

Br J Cancer. 2008 Oct 7;99(7):1013-9. doi: 10.1038/sj.bjc.6604667. Epub 2008 Sep 16.

Abstract

The significance of the inter-relationship between tumour and host local/systemic inflammatory responses in primary operable invasive breast cancer is limited. The inter-relationship between the systemic inflammatory response (pre-operative white cell count, C-reactive protein and albumin concentrations), standard clinicopathological factors, tumour T-lymphocytic (CD4+ and CD8+) and macrophage (CD68+) infiltration, proliferative (Ki-67) index and microvessel density (CD34+) was examined using immunohistochemistry and slide-counting techniques, and their prognostic values were examined in 168 patients with potentially curative resection of early-stage invasive breast cancer. Increased tumour grade and proliferative activity were associated with greater tumour T-lymphocyte (P<0.05) and macrophage (P<0.05) infiltration and microvessel density (P<0.01). The median follow-up of survivors was 72 months. During this period, 31 patients died; 18 died of their cancer. On univariate analysis, increased lymph-node involvement (P<0.01), negative hormonal receptor (P<0.10), lower albumin concentrations (P<0.01), increased tumour proliferation (P<0.05), increased tumour microvessel density (P<0.05), the extent of locoregional control (P<0.0001) and limited systemic treatment (P<or=0.01) were associated with cancer-specific survival. On multivariate analysis of these significant covariates, albumin (HR 4.77, 95% CI 1.35-16.85, P=0.015), locoregional treatment (HR 3.64, 95% CI 1.04-12.72, P=0.043) and systemic treatment (HR 2.29, 95% CI 1.23-4.27, P=0.009) were significant independent predictors of cancer-specific survival. Among tumour-based inflammatory factors, only tumour microvessel density (P<0.05) was independently associated with poorer cancer-specific survival. The host inflammatory responses are closely associated with poor tumour differentiation, proliferation and malignant disease progression in breast cancer.

摘要

肿瘤与宿主局部/全身炎症反应之间的相互关系在原发性可手术浸润性乳腺癌中的意义有限。使用免疫组织化学和玻片计数技术研究了全身炎症反应(术前白细胞计数、C反应蛋白和白蛋白浓度)、标准临床病理因素、肿瘤T淋巴细胞(CD4 +和CD8 +)及巨噬细胞(CD68 +)浸润、增殖(Ki-67)指数和微血管密度(CD34 +)之间的相互关系,并在168例可能治愈性切除的早期浸润性乳腺癌患者中检测了它们的预后价值。肿瘤分级增加和增殖活性增强与肿瘤T淋巴细胞浸润增加(P<0.05)、巨噬细胞浸润增加(P<0.05)和微血管密度增加(P<0.01)相关。幸存者的中位随访时间为72个月。在此期间,31例患者死亡;18例死于癌症。单因素分析显示,淋巴结受累增加(P<0.01)、激素受体阴性(P<0.10)、白蛋白浓度降低(P<0.01)、肿瘤增殖增加(P<0.05)、肿瘤微血管密度增加(P<0.05)、局部区域控制程度(P<0.0001)和全身治疗有限(P≤0.01)与癌症特异性生存相关。对这些显著协变量进行多因素分析时,白蛋白(HR 4.77,95%CI 1.35 - 16.85,P = 0.015)、局部区域治疗(HR 3.64,95%CI 1.04 - 12.72,P = 0.043)和全身治疗(HR 2.29,95%CI 1.23 - 4.27,P = 0.009)是癌症特异性生存的显著独立预测因素。在基于肿瘤的炎症因素中,只有肿瘤微血管密度(P<0.05)与较差的癌症特异性生存独立相关。宿主炎症反应与乳腺癌中肿瘤分化差、增殖及恶性疾病进展密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8e89/2567062/561508983314/6604667f1.jpg

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