Decreased number of mast cells infiltrating into needle biopsy specimens leads to a better prognosis of prostate cancer

Abstract

Mast cell infiltration is often observed around human tumours. Inflammatory cells such as macrophages, neutrophils and mast cells infiltrating around tumours are known to contribute to tumour growth; however, the clinical significance of mast cell invasion in prostate cancer (PCa) has not been investigated. Mast cell infiltration was evaluated in 104 patients (age range, 45 -88 years; median, 72 years), who underwent needle biopsy of the prostate and were confirmed to have PCa. Needle biopsy specimens of prostate were sliced into 5-mm-thick sections and immunostained for mast cells with monoclonal antibody against mast cell-specific tryptase. Mast cells were counted systematically under a microscope ( Â 400 magnification), and the relations between mast cell numbers and clinicopathologic findings were evaluated. The mast cell count was evaluated for prognostic value by multivariate analysis. Mast cells were immunostained around the cancer foci. The median number of mast cells in each case was 16. The mast cell count was higher around cancer foci in patients with higher Gleason scores than in those with low Gleason scores. The mast cell number correlated well with clinical stage (Po0.001). Prostate-specific antigen-free survival of patients with higher mast cell counts was better than that in patients with lower mast cell counts (Po0.001). Multivariate analysis revealed that mast cell count was a significant prognostic factor (Po0.005). The number of mast cells infiltrating around cancer foci in prostate biopsy specimens can be a significant prognostic factor of PCa.

Mast Cells Are Novel Independent Prognostic Markers in Prostate Cancer and Represent a Target for Therapy

“…This could explain the contradictory findings regarding mast cell function in PC by other researchers [12][13] and are in line with the described plasticity of the role of mast cells in tumor biology. 8 -11 Mast cells produce a broad repertoire of cytokines to regulate inflammatory responses, growth factors to stimulate blood vessels and fibroblasts, and enzymes capable of releasing growth factors from extracellular matrix.…”

“…[12][13] In both nonmalignant and malignant human prostate tissue, mast cells were found principally in the stroma. In prostate tumors only a few mast cells were detected in the epithelial compartment ( Figure 4, A and B).…”

“…One of the studies showed that tryptase-positive mast cells were related to poor outcome in PC patients. 12 The other study analyzed c-Kit-positive cells in tumor samples from PC patients and found an association between increased mast cell numbers and a favorable prognosis. …”

In colorectal cancer mast cells contribute to systemic regulatory T-cell dysfunction

“…In contrast, the frequency of Foxp3 + cells with low cell surface CD25 was similar in the tumor and marginal tissue ( CRC Tumors Are Enriched in MC. Numerous reports exist of accumulation of MC in tumors, but only recently has this accumulation been convincingly linked with poor prognosis (22,23) and experimentally associated with carcinogenesis (4-6), as reviewed elsewhere (2, 3). Our earlier study suggested that there is a 3-fold enrichment of MC in human polyps compared with marginal tissue (4).…”

Mast cells are an essential hematopoietic component for polyp development

“…While this manuscript was under review, Soucek et al (58) reported that MC are required for the expansion of myc-induced pancreatic tumors, and Nonomura et al (59) reported a positive correlation between the frequency of MC in human prostate cancer needle biopsy specimens and poor prognosis.…”