Predictive value of PTEN and AR co-expression of sustained responsiveness to hormonal therapy in prostate cancer – A pilot study.

Soha S El Sheikh, Hanna M. Romanska, Paul Abel, Jan DOMIN and El-Nasir Lalani

Year 2008, Volume 10, Issue 9

Abstract

One important limitation of current biochemical or histological analysis of advanced prostate cancer (PC; T3/T4 ± NxMx) is the ability to identify on first diagnostic biopsy patients who will make a durable response to hormone ablation therapy. The aim of this paper was to assess the predictive value of immunohistochemical expression of tumour suppressor Phosphatase and Tensin homologue PTEN and/or androgen receptor (AR) in the initial PC biopsy for predicting sustained response to hormonal therapy and clinical outcome (relapse free and overall survival). Analysis was performed on a total of 47 samples (10 cases of BPH and 37 hormone-naïve prostate cancers). The PC patients representing two points in the natural history of PC: i) the ‘clinical metastatic androgen responsive’ (ADPC) and ii) the ‘clinical metastatic androgen resistant’ (AIPC) stages were selected for the study. Reduced immunoreactivity (IR) of either or both PTEN and AR in the initial hormone naïve PC samples was observed with an increased frequency in AIPCs. In ADPC group, low PTEN- and/or AR-IR was associated with a shorter median relapse-free survival, i.e., at 30 months after surgery, the probability of relapse-free survival for high-expressors of PTEN and AR was 85.7 % (SEM = 9.3) compared to only 16.6% (SEM = 15.2) in low-expressors. At 36 months, only 28.5% (SEM= 9.3) of ADPC high-expressors had suffered a biochemical relapse compared to 100% of low-expressors (hazard ratio 4.6 [95% CI = 4.7 to 146.8]). Further investigation analysing the co-expression of PTEN and AR should be undertaken to validate our pilot study and to assess a potential usefulness of this combined parameter as an additional marker in the routine histopathological workup of patients with PC enabling better prognostication of their responses to AAT.

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