Evaluation of combined cytoplasmic AR in tumour cells expression and tumour CD3 T-cells infiltrate as a prognostic score for patients with prostate cancer
V. Constâncio1,2,, , M. McAllister2, S. Patek2, M. Underwood3, H. Leung4, J. Edwards2
1 Biology Department, University of Aveiro, Portugal
2 Institute of Cancer Sciences, Wolfson Wohl Cancer Research Centre, University of Glasgow, United Kingdom
3 Department of Urology, Queen Elizabeth University Hospital, Glasgow, United Kingdom
4 Beatson Institute of Cancer Research, United Kingdom

Aim: We aimed to assess the prognostic value of using a cumulative score evaluating the expression of Androgen Receptor (AR) and the presence tumour inflammatory infiltrate as a prognostic marker for prostate cancer (PCa).

Introduction: PCa is the most common male cancer, in Europe. Currently, at diagnosis, only tumour-based factors, including clinical stage, tumour grade and circulating concentrations of Prostate-Specific Antigen (PSA) are used to predict PCa outcome. However, this can vary within patients sharing the same clinical conditions, leading to patient's over/under treatment. It is now recognized that cancer progression is also dependent on tumour's interaction with its microenvironment, specifically with immune cells. Therefore, the development of predictive biomarkers, capable of combining these two factors should be considered.

Methods: Immunohistochemistry for AR expression and CD3 T-cells was performed on biopsies from a cohort of 361 patients diagnosed with PCa. Semi-quantitative weighted histoscore and quantitative assessments were used.

Results: High cytoplasmic AR expression in tumour cells and high CD3-T cells presence were associated with reduced overall survival (p=0.000055, and p=0.004, respectively), with strong association (p=0.001) on X2 analysis. When patients were grouped as having: both markers low or one low and low/moderate and one high, and both high, this cumulative prognostic score was strongly associated with overall survival (p=0.000001), being the mean overall survivals: 7.1 years (95% CI 6.5–7.6), 6.0 years (95% CI 5.4–6.6) and 3.8 years (95% CI 2.4–5.0), respectively. Moreover, on multivariate analysis, it was considered a significant independent predictor of overall survival (HR 1.982, 95% CI 1.018–3.859, p=0.044).

Conclusion: These results confirm the clinical utility of assessing both tumour and microenvironment characteristics when predicting patients’ outcome, and suggest that the presence of high cytoplasmic AR expression in tumour cells and CD3 T-cells predicts poor outcome for patients diagnosed with PCa.

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