[Endothelin-1 and receptor A: predictive value for biochemical relapse on patients with advanced and metastatic...

Pathological endothelin axis is known to be involved in prostate cancer progression. Our study evaluates immunohistochemical expression of ET-1 and ET-AR on prostate biopsy specimen and the predictive value for biochemical relapse on patients with advanced and metastatic cancer. We also evaluated the impact of ET-1 and ET-AR expression on local progression and metastatic bone progression for these patients.

From 1992 to June 2009, 44 patients with clinical T3 stage and metastatic lymph nodes were included. PSA levels, Gleason score in biopsy cores, number of invaded lymph nodes, the existence of nodular capsule transgression and hormonal treatment given to the patient, were analyzed. Biopsy cores were submitted to immunohistochemical study of the expression of ET-1 and ET-AR. Semi-quantitative ET-1 and ET-AR staining assessment was always realised by the same pathologist.

The average age of the cohort was 65.6 (standard deviation 6.3), median PSA level was 52.8 ng /ml (3-227), median time of follow-up was 70 months (6-144). Biochemical relapse was observed in 62.8%. Statistically significant stronger ET-1 expression was observed in biopsies of patients with a biochemical relapse (p=0.014). Eighty percent of patients with a biochemical relapse had a high level of ET-AR expression, but no statistical significance has been shown (p=0.109). The relative risk for progression under hormonal therapy was 1.9 in case of high level of ET-1 expression and biochemical relapse was confirmed 8 months earlier in average. High level of ET-AR expression on biopsy cores may indicate earlier local progression and metastatic bone progression but there were no statistical proof.

In our study, the strength of ET-1 expression in prostate cancer biopsy cores is a prognostic factor of biochemical relapse for cT3 stage patients with metastatic lymph nodes. We have not been able to prove that ET-1 is an independent prognostic factor. A high level of ET-AR expression on prostate biopsy cores is not, in our study, a prognosis factor for predicting the biochemical relapse.