Tumor associated macrophages in human prostate cancer: relation to clinicopathological variables and survival

Tumor associated macrophages (TAM) influence diverse processes such as angi ogenesis, tumor cell proliferation, and metastasis during tumor progression . In a variety of tumor types, the amount of TAM has been associated with p rognosis, but their role in prostate cancer has not been elucidated. The pu rpose of this study was to investigate the role of TAM in a series of 85 ca ses of prostatic carcinoma, diagnosed at transurethral resection of the pro state between 1975-1983, using immunohistochemistry and morphometrical tech niques. Macrophage density was assessed as the maximum number of TAM per fi eld in the three most macrophage dense areas (TAM(max)) and as the average volume density of TAM in an estimate of the whole resected tumor. Furthermo re, the individual cell profile area of TAM was assessed with an image anal yzer. Macrophage variables were thereafter related to histological grade, t umor stage, metastasis as well as to vascular density, tumor cell prolifera tion and survival. Patients with a volume density of TAM in the fourth quar tile had a shorter median cancer specific survival time than patients in th e first to third quartile (3.3 vs. 5.9 years, p=0.005). Furthermore, an inc reased macrophage cell profile area was related to poor clinical outcome (4 .6 vs. 5.9 years, p=0.039) whereas TAM(max) gave no prognostic information. In a multivariate analysis, metastasis and the volume density of macrophag es gave independent prognostic information (p=0.0008, p=0.010). However, wh en excluding metastasis from the analysis, only Gleason score was an indepe ndent predictor of cancer specific survival (p=0.005). The volume density o f TAM, the macrophage cell profile area and TAM(max) increased with increas ing Gleason score (p=0.001, p=0.0001, p=0.0001 respectively). A correlation was found between the volume density of TAM and tumor cell proliferation ( r(s)=0.44, p=0.001) and an increased macrophage cell profile area was assoc iated to microvessel density (r(s)=0.42, p=0.0001). Together these results suggest that both the functional state (as reflected by cell size), number and location of the macrophages are of importance for their influence on pr ostate tumors, but macrophage quantification is not a strong independent pr ognostic factor.