Increased Infiltration of Tumor Associated Macrophages is Associated With Poor Prognosis of Bladder Carcinoma In Situ After Intravesical Bacillus Calmette-Guerin Instillation

Abstract

Tumor associated macrophages can regulate the growth of various cancers positively or negatively. Intravesical bacillus Calmette-Guerin instillation is now gold standard treatment for bladder carcinoma in situ. We investigated the correlation between tumor associated macrophages infiltrating bladder carcinoma in situ and the response to intravesical bacillus Calmette-Guerin therapy. We examined paraffin embedded tissues from 41 patients with bladder carcinoma in situ who received intravesical bacillus Calmette-Guerin therapy. Tumor associated macrophages were immunohistochemically stained by anti-CD68 monoclonal antibody. The median number of tumor associated macrophages infiltrating among cancer cells and the number in the lamina propria were 4 and 24, respectively. Recurrent carcinoma in situ was found in 4.8% of cases with a lower cancer cell tumor associated macrophage count but in 47.6% of those with a higher cancer cell tumor associated macrophage count (less than 4 vs 4 or greater). Recurrence was found in 31.8% of patients with a lower lamina propria tumor associated macrophage count but in 21.1% of those with a higher lamina propria tumor associated macrophage count (less than 25 vs 25 or greater). The median ratio of tumor associated macrophages among cancer cells vs in the lamina propria was 0.2. Recurrence-free survival was significantly better in patients with a lower cancer cell tumor associated macrophage count (p = 0.0002). Those with a lower cancer cell-to-lamina propria tumor associated macrophage ratio had a higher recurrence-free rate (p <0.0001). Multivariate analysis revealed that the cancer cell tumor associated macrophage count and the cancer cell-to-lamina propria tumor associated macrophage ratio can be prognostic factors for bladder carcinoma in situ. The count of tumor associated macrophages infiltrating the cancer area is useful for predicting the response of bladder carcinoma in situ to intravesical bacillus Calmette-Guerin instillation before treatment initiation.