Reduced infiltration of tumor-associated macrophages in human prostate cancer: Association with cancer progression

Tumor-associated macrophages (TAMs) are highly active immune effector cells that may either positively or negatively regulate the growth of various ma lignant cells, depending on the biological context. However, the role of TA Ms in human prostate ranter progression is unclear. TAMs were immunohistoch emically labeled using a monoclonal (CD68) antibody in radical prostatectom y specimens derived from 81 prostate cancer patients. CD68-positive cells w ere counted with the aid of a microscope and expressed as macrophage index (MphiI), including TAMs/mm(2) total tumor tissue (M phiI(total)), TAMs/mm(2 ) tumor stroma (MphiIstroma), and TAMs/mm(2) cancer cell area (MphiIcancer) . M(phi)Is were analyzed in association with patients' clinical and patholo gical 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 MphiIto tal was also associated with the presence of positive lymph nodes (P = 0.01 0). Interestingly, although all of the M(phi)Is differed between Gleason sc ore groups, only MphiIcancer was positively associated with Gleason score. Univariate analyst of MphiItotal and multivariate analysis of M phiI(total) with specific pathological markers revealed that MphiItotal was an indepen dent predictor for disease-free survival after surgery (Cox proportional ha zard model, P = 0.044 and P = 0.007, respectively). For patients with high MphiItotal (greater than or equal to 185.8, the mean MphiItotal value), the disease-free probability 5 years after surgery was 0.75, which was signifi cantly higher than fur those with low M phiI(total) (0.31, P = 0.0008). Add itional immunohistochemical studies that evaluated cytotoxicity-related bio markers in stroma-associated mononuclear cells suggested reduced functional activities in highly aggressive prostate cancer compared with less aggress ive disease. Our results indicate that reduced MphiItotal is a novel progno stic marker for prostate cancer.