Alternatively activated macrophages are associated with metastasis and poor prognosis in prostate adenocarcinoma

Abstract

Recent studies have revealed that alternatively activated macrophages (AAMs) are involved in tumor progression. However, the effect of AAMs on the metastasis of prostate cancer is poorly understood. In the present study, the prostate tissues of 42 patients with prostate adenocarcinoma (PCa) were used in the analysis of tumor associated macrophages (TAMs) and AAMs by immunofluorescence. The patients were followed up for 5 years. The associations of TAMs and AAMs with the clinicopathological features and outcome in these cases were evaluated. Immunofluorescent analysis indicated that the mean number of TAMs (CD68-positive cells) in the prostate tissues of PCa patients with metastasis [45.29±7.25 cells/high-power field (HPF)] was significantly higher compared with that of PCa patients without metastasis (33.57±5.25 cells/HPF; P<0.01). The mean numbers of AAMs (CD68- and CD206-positive cells) in the tissues of PCa patients with and without metastasis were 29.43±5.68 and 9.14±5.29 cells/HPF, respectively. In addition, the percentage of AAMs (number of AAMs/number of TAMs) was 65.11±9.68 and 27.32±7.85% in patients with and without metastasis, respectively. The differences in the number and percentage of AAMs between the two groups were statistically significant (P<0.01). The number and percentage of AAMs was positively correlated with tumor grade and serum prostate-specific antigen (PSA) level. Univariate analysis indicated that the level of PSA, Gleason score, metastatic status, T grade, number of TAMs, number of AAMs and percentage of AAMs were predictors of the overall survival. Furthermore, multivariate analyses revealed that Gleason score, level of PSA and number of TAMs were predictors for overall survival rate. These results indicate that TAMs and AAMs may be important in the metastasis of PCa, and that TAMs and AAMs may be used as potential biomarkers of poor prognosis in late-stage PCa patients.

Keywords: alternatively activated macrophage; metastasis; prognosis; prostate adenocarcinoma; tumor associated macrophage.

Figure 1.

AAMs in prostate tissues of PCa patients with or without metastasis. (A) Confocal photomicrographs (magnification, x800) reveal the number of TAMs (CD68-positive cells) and AAMs (co-localization signals of CD68 and CD206) are significantly higher than that of PCa patients without metastasis. Blue corresponds to nuclear staining, green corresponds to CD68 staining and red corresponds to CD206 staining. (B) Number and percentage of AAMs in prostate tissues of PCa patients. Results are presented as the mean ± standard error of the mean for a group of 21 patients. *P<0.01. PCa, prostate adenocarcinoma; TAM, tumor-associated macrophage; AAM, alternatively activated macrophage; HPF, high-power field.

Figure 2.

Kaplan-Meier analysis of overall survival. Survival curves demonstrate the association between overall survival following diagnosis and the (A) level of TAMs, (B) level of AAMs and (C) percentage of AAMs. Statistically significant differences between the groups were estimated using χ² test. TAM, tumor-associated macrophage; AAM, alternatively activated macrophage.