C-MYC, HER2, and HER3 expression in localized prostate cancer (PC) treated with radical radiotherapy: Modulation by statins use and correlation with time to progression.

Abstract

e16045 Background: There has been growing interest in the activity of statins (St) in PC patients receiving definitive radiation therapy. The oncogene Ras can be inhibited by HMG-CoA reductase inhibitors that in turn are also able to downregulate Myc. The aim of this study was to correlate St use and progression with the c-Myc, HER2 and HER3 expression in PC treated with radical radiotherapy (RT) with concurrent androgen deprivation. Methods: A total of 85 patients diagnosed with localised PC between 2000 and 2005 were selected for the study. Inmunohistochemical assay on core biopsy of each patient was performed using monoclonal antibodies for c-Myc, HER2 and HER3. The expression was evaluated using a semiquantitative method (Hscore scale: 0 to 300). Clinical and pathological variables were compared between St users and non-users and correlated with expression of c-Myc, HER2 and HER3. St users were defined as patients who had been taking St for at least 2 years before the diagnosis of PC and during follow up. Time to progression (TTP) was analyzed. Results: Mean age was 71 (56-82) years. Median follow-up was 75 months after RT. Twenty-five patients (29.4%) were using St. No statistical differences were found between treatment groups regarding median age, risk category, clinical T stage, Gleason score or median radiation dose. Median Hscore value of c-Myc was 40 (5-210) for St users vs. 72.5 (5-280) for non-users (p = 0.01). Only 8.6% of the cases showed HER2 expression and in those staining was mild intense and focal. Moderate expression of HER3 was observed in 36 cases (41.8%) and no correlation with St users nor with TTP was demonstrated (p=0.8). At the time of analysis, only 13 pts (15.3%) had biochemical relapse (1 low risk, 3 intermediate, and 9 high risk). St use (46.2%) was significantly associated with improved TTP (55 vs. 36.2 months, p = 0.022). Conclusions: Our work implicates a correlation of St use with a significant lower c-Myc expression and improvement in TTP in all groups, regardless the risk. No correlation was reported between HER2 or HER3, TTP and St use.