Association between tumor-associated macrophage infiltration, high grade prostate cancer, and biochemical recurrence after radical prostatectomy

Background: Tumor-associated macrophages (TAMs) are a key component of the inflammatory microenvironment. Their role in prostate cancer development and progression remains unclear. We examined whether the amount of TAMs in prostate cancer is: 1) higher than prostatic intraepithelial neoplasia (PIN) and benign tissue 2) associated with poorly differentiated disease, and 3) predictive of biochemical recurrence among surgically treated men.

Methods: A tissue microarray (TMA) of prostatectomy specimens from 332 patients was stained for CD68, a TAM marker. A separate TMA was used for validation. Associations between mean TAMs in cancer cores and PSA recurrence were determined by Cox proportional hazards models after adjusting for age, preoperative PSA, race, body mass index, pathologic Gleason sum, seminal vesicle invasion, extracapsular extension, and margin status.

Results: Mean TAM number was higher in cancer versus PIN and benign tissue (p<0.0001). Mean TAM number was higher in Gleason grade 4 cores vs. Gleason grade 3 cores (p=0.003). On multivariable analysis, no association was observed between mean TAM number per cancer core and biochemical recurrence in either cohort.

Conclusion: Mean TAM number was higher in cancer cores vs. PIN and benign tissue, and higher in high grade prostate cancer supporting the potential role of TAMs in prostate cancer development. However, TAMs were not associated with biochemical recurrence after radical prostatectomy suggesting TAM counts do not provide independent prognostic value among surgically treated men. Further studies are required to elucidate the functional significance of TAMs in the prostate cancer microenvironment.