Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression.
Reduced infiltration of tumor-associated macrophages in human prostate cancer: association with cancer progression.
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发表时间：
2000-10
期刊：
影响因子：
11.2
通讯作者：
S. Shimura;Guang Yang;Shin Ebara;Thomas M. Wheeler;A. Frolov;T. Thompson
中科院分区：
文献类型：
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作者：
S. Shimura;Guang Yang;Shin Ebara;Thomas M. Wheeler;A. Frolov;T. Thompson
肿瘤相关巨噬细胞（TAM）是高度活跃的免疫效应细胞，其可以根据生物学背景正向或负向调节各种恶性细胞的生长。然而，TAM在人类前列腺癌进展中的作用尚不清楚。TAM使用单克隆（CD 68）抗体在来自81例前列腺癌患者的根治性前列腺切除术标本中进行化学标记。借助显微镜对CD 68阳性细胞进行计数，并表示为巨噬细胞指数（MphiI），包括TAM/mm 2总肿瘤组织（MphiI总）、TAM/mm 2肿瘤基质（MphiI基质）和TAM/mm 2癌细胞面积（MphiI癌）。分析MphiIs与患者的临床和病理分期、复发状态和癌症的组织学分级的关系。MphiItotal和MphiIstroma与临床分期呈显著负相关（分别为P = 0.016和P = 0.006）。MphiItotal降低也与阳性淋巴结的存在相关（P = 0.010）。有趣的是，尽管所有的MphiI在Gleason评分组之间不同，但只有MphiI癌症与Gleason评分呈正相关。MphiItotal的单变量分析和MphiItotal与特定病理标志物的多变量分析显示，MphiItotal是手术后无病生存的独立预测因子（考克斯比例风险模型，分别为P = 0.044和P = 0.007）。对于高MphiItotal（≥ 185.8，平均MphiItotal值）的患者，术后5年的无病概率为0.75，显著高于低MphiItotal的患者（0.31，P = 0.0008）。评估基质相关单核细胞中细胞毒性相关生物标志物的其他免疫组织化学研究表明，与侵袭性较低的疾病相比，高度侵袭性前列腺癌的功能活动减少。我们的研究结果表明，减少MphiItotal是一种新的前列腺癌的预后标志物。
Tumor-associated macrophages (TAMs) are highly active immune effector cells that may either positively or negatively regulate the growth of various malignant cells, depending on the biological context. However, the role of TAMs in human prostate cancer progression is unclear. TAMs were immunohistochemically labeled using a monoclonal (CD68) antibody in radical prostatectomy specimens derived from 81 prostate cancer patients. CD68-positive cells were counted with the aid of a microscope and expressed as macrophage index (MphiI), including TAMs/mm2 total tumor tissue (MphiItotal), TAMs/mm2 tumor stroma (MphiIstroma), and TAMs/mm2 cancer cell area (MphiIcancer). MphiIs were analyzed in association with patients' clinical and pathological stage, recurrence status, and histological grade of the cancer. There were significant inverse relationships between MphiItotal and MphiIstroma and clinical stage (P = 0.016 and P = 0.006, respectively). Reduced MphiItotal was also associated with the presence of positive lymph nodes (P = 0.010). Interestingly, although all of the MphiIs differed between Gleason score groups, only MphiIcancer was positively associated with Gleason score. Univariate analysis of MphiItotal and multivariate analysis of MphiItotal with specific pathological markers revealed that MphiItotal was an independent predictor for disease-free survival after surgery (Cox proportional hazard model, P = 0.044 and P = 0.007, respectively). For patients with high MphiItotal (> or = 185.8, the mean MphiItotal value), the disease-free probability 5 years after surgery was 0.75, which was significantly higher than for those with low MphiItotal (0.31, P = 0.0008). Additional immunohistochemical studies that evaluated cytotoxicity-related biomarkers in stroma-associated mononuclear cells suggested reduced functional activities in highly aggressive prostate cancer compared with less aggressive disease. Our results indicate that reduced MphiItotal is a novel prognostic marker for prostate cancer.