Infiltration of tumour‐associated macrophages in prostate biopsy specimens is predictive of disease progression after hormonal therapy for prostate cancer

Abstract

Study Type – Prognostic (case series) Level of Evidence 4 What’s known on the subject? and What does the study add? In general, tumour‐associated macrophage (TAM) is important for tumour progression including prostate cancer. In this paper, we clarified the usefulness of TAM in prostate biopsy specimens for predicting prognosis after hormonal therapy. OBJECTIVE • To evaluate tumour‐associated macrophage (TAM) infiltration in prostate biopsy specimens as a possible prognostic factor for prostate cancer (PCa) after hormonal therapy. PATIENTS AND METHODS • Immunostaining of TAMs in prostate biopsy specimens was performed using a monoclonal antibody CD68 for 71 patients having PCa treated with hormonal therapy. • Six microscopic (×400) fields around the cancer foci were selected for TAM counting. RESULTS • The median value of serum prostate‐specific antigen (PSA) was 50.1 ng/mL, and the median TAM count was 22. • Recurrence‐free survival was significantly better in patients with fewer TAMs (<22) than in those with higher numbers of TAMs (≥22) (P < 0.001). • TAM count was higher in those with higher serum PSA (PSA), higher Gleason score, clinical T stage or those with PSA failure. Cox multivariate analysis showed that TAM count is one of the prognostic factors for PCa treated by hormonal therapy (P < 0.0001). CONCLUSION • TAM infiltration in prostate needle biopsy specimens is a useful predictive factor for PSA failure or progression of PCa after hormonal therapy.

Prognostic value of twist-1, e-cadherin and ezh2 in prostate cancer: an immunohistochemical study

“…Regarding the association between the prognostic parameters and biochemical progression in our study, we found a significant association between the conventional parameters including the initial PSa level, gleason score ≥7, and tumor tNM stage with biochemical progression as previously reported by other investigators (37)(38)(39). In addition, early biochemical recurrence was more prevalent in cases with high twist-1, aberrant E-cadherin, and high EZH2 expression.…”

Identification of Differentially Expressed Proteins in Direct Expressed Prostatic Secretions of Men with Organ-confined Versus Extracapsular Prostate Cancer

“…Lymphocytes and macrophages present in the prostate are most often associated with this chronic inflammation, and less frequently plasma cells, eosinophils, and neutrophils (63,64). The presence of tumor-associated macrophages have been reported as potential biomarkers of poor prognosis in prostate cancers (65,66), and we have evidence that these macrophages can be detected by flow cytometry of the low speed cell pellets of EPS urine samples in a subset of prostate cancer patients (data not shown). A better understanding of the role of the many detectable biomarkers of immune system activity, like the members of the complement pathway overexpressed in nonorgan-confined EPS samples, is critical for improving diagnostic targeting of aggressive prostate cancers.…”

The Role of Inflammation in Prostate Cancer

“…This same group later reported that lower numbers of prostate-infiltrating class A macrophage scavenger receptor (SR-A)-expressing cells (dendritic cells and macrophages) were similarly associated with higher clinical stage and positive lymph nodes and predictive of shorter time to PSA progression (Yang et al 2004). Although the intriguing positive association of macrophage numbers with Gleason score has held up in multiple additional studies, TAM quantification as an independent prognostic factor Hao et al (2012) for time to PSA progression has varied (Lissbrant et al 2000;Wang et al 2005;Nonomura et al 2011). In a study on disease progression after hormone therapy for prostate cancer, TAM densities as assayed by IHC for CD68 on patient's prostate biopsy specimens prior to treatment were found to be positively correlated with Gleason score and clinical stage (Nonomura et al 2011).…”

“…Although the intriguing positive association of macrophage numbers with Gleason score has held up in multiple additional studies, TAM quantification as an independent prognostic factor Hao et al (2012) for time to PSA progression has varied (Lissbrant et al 2000;Wang et al 2005;Nonomura et al 2011). In a study on disease progression after hormone therapy for prostate cancer, TAM densities as assayed by IHC for CD68 on patient's prostate biopsy specimens prior to treatment were found to be positively correlated with Gleason score and clinical stage (Nonomura et al 2011). Furthermore, in contrast to the studies by Shimura et al (2000) and Yang et al (2004), Nonomura et al reported that increased numbers of TAMs were significantly associated with PSA progression and serve as a prognostic indicator for decreased time to progression-free survival (Nonomura et al 2011).…”