Shimura S, Yang G, Ebara S, Wheeler T M, Frolov A, Thompson T C
Scott Department of Urology, Baylor College of Medicine, Houston, Texas 77030, USA.
Cancer Res. 2000 Oct 15;60(20):5857-61.
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.
肿瘤相关巨噬细胞（TAMs）是高度活跃的免疫效应细胞，根据生物学背景，它们可能对各种恶性细胞的生长产生正向或负向调节作用。然而，TAMs在人类前列腺癌进展中的作用尚不清楚。在来自81例前列腺癌患者的根治性前列腺切除标本中，使用单克隆（CD68）抗体对TAMs进行免疫组织化学标记。借助显微镜对CD68阳性细胞进行计数，并表示为巨噬细胞指数（MphiI），包括每平方毫米总肿瘤组织中的TAMs（MphiItotal）、每平方毫米肿瘤基质中的TAMs（MphiIstroma）和每平方毫米癌细胞区域中的TAMs（MphiIcancer）。分析MphiI与患者的临床和病理分期、复发状态以及癌症组织学分级之间的关系。MphiItotal和MphiIstroma与临床分期之间存在显著的负相关（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MphiI在Gleason评分组之间存在差异，但只有MphiIcancer与Gleason评分呈正相关。对MphiItotal的单因素分析以及对MphiItotal与特定病理标志物的多因素分析显示，MphiItotal是手术后无病生存的独立预测指标（Cox比例风险模型，分别为P = 0.044和P = 0.007）。对于MphiItotal较高（≥185.8，MphiItotal平均值）的患者，术后5年的无病概率为0.75，显著高于MphiItotal较低的患者（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额外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中的功能活性降低。我们的结果表明，MphiItotal降低是前列腺癌的一种新的预后标志物。
