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人食管鳞状细胞癌中肿瘤相关巨噬细胞及肿瘤浸润淋巴细胞的CD3-ζ表达

Tumor-associated macrophages and CD3-zeta expression of tumor-infiltrating lymphocytes in human esophageal squamous-cell carcinoma.

作者信息

Guo S-J, Lin D-M, Li J, Liu R-Z, Zhou C-X, Wang D-M, Ma W-B, Zhang Y-H, Zhang S-R

机构信息

Department of Immunology, Cancer Institute & Cancer Hospital, Peking Uninion Medical College and Chinese Academy of Medical Sciences, Beijing, PR China.

出版信息

Dis Esophagus. 2007;20(2):107-16. doi: 10.1111/j.1442-2050.2007.00655.x.

DOI:10.1111/j.1442-2050.2007.00655.x
PMID:17439593
Abstract

The clinical significance of tumor-associated macrophages (TAMs) and CD3-zeta chain expression of tumor-infiltrating lymphocytes (TILs), and their correlation in human esophageal squamous cell carcinoma (SCC) are not very clear. Serial histological slides from 137 esophageal SCC patients who had undergone tumor resection were immunohistochemically studied with anti-CD68, anti-CD3-zeta and anti-CD3-epsilon antibodies. TAMs infiltration (expressed as macrophage index, M(phi)I) and CD3-zeta expression (judged by Z/E = CD3-zeta+ cells/CD3-epsilon+ cells ratio) in different tissue compartments were observed. We found that the total tumor tissue region had significantly higher macrophage density and lower CD3-zeta expression (mean +/- SD: M(phi)I(normal): 225.3 +/- 85.9; Z/E(total): 0.52 +/- 0.25; n = 137) relative to adjacent histologically normal esophageal squamous epithelium (M(phi)I(normal): 60.5 +/- 31.7, P < 0.001; Z/E(normal): 0.79 +/- 0.35, P = 0.001; n = 70). Significantly higher M(phi)I(stroma) (P = 0.006) and lower Z/E(total) (P = 0.016) were detected in patients with lymph node metastasis than in those without. Patients with high M(phi)I(total) and M(phi)I(cancer) but low Z/E(total) had poorer surgical outcomes. Univariate analysis of M(phi)I(total) and multivariate analysis of M(phi)I(total) with specific clinico-pathological parameters demonstrated M(phi)I(total) to be an independent prognostic factor for survival in esophageal SCC patients (Cox proportional hazard model, P = 0.029 and P = 0.031, respectively).

摘要

肿瘤相关巨噬细胞(TAM)和肿瘤浸润淋巴细胞(TIL)的CD3-ζ链表达在人类食管鳞状细胞癌(SCC)中的临床意义及其相关性尚不完全清楚。对137例行肿瘤切除术的食管SCC患者的系列组织学切片进行免疫组织化学研究,采用抗CD68、抗CD3-ζ和抗CD3-ε抗体。观察不同组织区域的TAM浸润(以巨噬细胞指数,M(ϕ)I表示)和CD3-ζ表达(通过Z/E = CD3-ζ+细胞/CD3-ε+细胞比值判断)。我们发现,相对于相邻组织学正常的食管鳞状上皮,肿瘤组织整体区域的巨噬细胞密度显著更高,而CD3-ζ表达更低(均值±标准差:M(ϕ)I(正常):225.3±85.9;Z/E(整体):0.52±0.25;n = 137)(M(ϕ)I(正常):60.5±31.7,P < 0.001;Z/E(正常):0.79±0.35,P = 0.001;n = 70)。有淋巴结转移的患者中,M(ϕ)I(基质)显著更高(P = 0.006),而Z/E(整体)更低(P = 0.016)。M(ϕ)I(整体)和M(ϕ)I(癌)高但Z/E(整体)低的患者手术结局较差。对M(ϕ)I(整体)进行单因素分析以及将M(ϕ)I(整体)与特定临床病理参数进行多因素分析,结果显示M(ϕ)I(整体)是食管SCC患者生存的独立预后因素(Cox比例风险模型,P分别为0.029和0.031)。

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