Altered expression of farnesyl pyrophosphate synthase in prostate cancer: evidence for a role of the mevalonate pathway in disease progression?

• Published in: World journal of urology Vol. 31; no. 2; pp. 345 - 350
• Main Authors: Todenhöfer, Tilman, Hennenlotter, Jörg, Kühs, Ursula, Gerber, Valentina, Gakis, Georgios, Vogel, Ulrich, Aufderklamm, Stefan, Merseburger, Axel, Knapp, Judith, Stenzl, Arnulf, Schwentner, Christian
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer-Verlag 01.04.2013; Springer Nature B.V
• Subjects: Aged; Disease Progression; Disease-Free Survival; Geranyltranstransferase - metabolism; Humans; Male; Medicine; Medicine & Public Health; Mevalonic Acid - metabolism; Middle Aged; Multivariate Analysis; Neoplasm Grading; Neoplasm Staging; Nephrology; Oncology; Original Article; Prognosis; Prostate - enzymology; Prostate - pathology; Prostatic Neoplasms - enzymology; Prostatic Neoplasms - pathology; Risk Factors; Tissue Array Analysis; Urology; Zoledronic acid; Farnesyl pyrophosphate synthase; Prostate cancer; Bisphosphonates; Mevalonate pathway
• ISSN: 0724-4983; 1433-8726
• DOI: 10.1007/s00345-012-0844-y

Background Preclinical studies demonstrated effects of drugs inhibiting the mevalonate pathway including nitrogen-containing bisphosphonates (N-BPs) and statins on tumor growth and progression. The exact role of this pathway in prostate cancer (PC) has not been identified yet. Herein, we evaluate the expression of farnesyl pyrophosphate synthase (FPPS), the key enzyme of the mevalonate pathway, in PC. Patients and methods Prostate cancer (PC) and benign prostate tissue of 114 men who underwent radical prostatectomy were constructed to a tissue microarray. Immunohistochemical staining of FPPS was quantified by the Remmele/Stegner immunoreactivity-score. Patients’ clinical follow-up was assessed. IRS was correlated to pathological and clinical data. The impact of FPPS expression on clinical course was assessed univariate and multivariate. Results Mean IRS in PC and benign tissue was 5.7 (95% CI 5.0–6.5) and 2.6 (2.1–3.0, p  < 0.0001). Mean IRS in PC tissue of patients with organ-confined and locally advanced disease (pT ≥ 3) was 5.09 (4.22–5.96) and 6.87 (5.57–8.17, p  = 0.035). IRS of PC tissue significantly correlated with Gleason score ( p  = 0.03). Patients with PC tissue IRS >3 showed shorter recurrence-free survival compared to the remaining ( p  = 0.01). Increased FPPS expression is an independent risk factor for early biochemical recurrence ( p  = 0.032). Conclusions This is the first study on FPPS in PC specimens. The association of FPPS with established histopathological risk parameters and biochemical recurrence implicates a contribution of the mevalonate pathway to PC progression. Further functional analysis is required to explore the role of this pathway in PC and to investigate whether FPPS expression affects the response of PC cells to N-BPs.