Abstract
In New Zealand, prostate cancer is the most common cancer in men. Māori men have significantly higher prostate cancer mortality than non-Māori men, and are more likely to be diagnosed with metastatic disease. Clinical management of prostate cancer is challenging because current prognostic techniques cannot determine whether the cancer is going to rapidly progress or remain dormant. Consequently, men are commonly under or over treated, and there is an urgent need for improved prognostic biomarkers for the disease.
Cancer-associated adipocytes (CAA) adopt an “activated phenotype” which can promote cancer cell invasion, metastasis, and progression. The prostate is surrounded by periprostatic adipose tissue (PPAT) which secretes factors that promote the progression of prostate cancer. Preliminary proteomic data obtained using in vitro transwell co-culture of breast cancer cells and primary human breast adipocytes identified seven candidate factors secreted by CAA, which are known to be present in prostate tumour or stroma (Dr E Phillips). The aim of this pilot study was to assess these seven candidate factors in prostate tumour tissue, and analyse expression together with clinicopathological markers of prostate cancer progression.
Two bespoke tissue-microarrays (TMAs) were constructed for analysis by immunostaining. Two tumour, one stroma and one adipose core were mined from each formalin fixed paraffin embedded prostate tumour sample (n=60). Immunohistochemistry was performed on consecutive sections (5μm) using primary antibodies against CCR3, CD304, HGFA, LOXL2, MMP14, OPN and uPA. Protein expression of each marker was scored manually (scale 0-3; staining intensity and % of cells staining) and using QuPath bioimage analysis software.
All markers were present in tumour, stroma, and adipose tissue. uPA and OPN showed the strongest staining in tumour, with CCR3 strongest in adipose tissue. Immunohistochemical analysis was combined with patient characteristics (Body Mass Index; BMI), tumour pathology (Prostate Specific Antigen; PSA, Gleason score) and clinical follow-up (biochemical recurrence). The expression of OPN, uPA and CD304 in adipose, and HGFA, LOXL2, MMP14, and OPN in stroma, was associated with clinicopathological indicators of worse outcomes in men with prostate cancer. This study highlights the importance of investigating the whole tumour microenvironment for potentially prognostic biomarkers for prostate cancer.