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Chromogranin A Expression In Patients With Hormone Naive Prostate Cancer Predicts The Development Of Hormone Refractory Disease

August 30, 2017

UroToday- Prostate cancer cells can undergo trans-differentiation to a neuroendocrine phenotype called neuroendocrine differentiation (NED). These cells then express neurokines or proteins similar to what nerve cells secrete. It is known that these neurokines can activate the androgen receptor in the absence of androgens and are one mechanism accounting for androgen independence. Chromogranin A (CgA) is one such neurokine that can be measured in prostate cancer (CaP) tissue by immunohistochemistry (IHC) or in serum. In the July 2007 early view of the Journal of Urology, Dr. Berruti and colleagues report that levels of CgA expression is an independent predictive factor for the development of androgen independent prostate cancer (AICaP).

Between 1996 and 2003 all patients with a positive CaP biopsy and intermediate or high risk disease had the biopsy tissue stained for CgA by IHC and serum levels measured for CgA by immunoassay. Patients were treated with androgen deprivation therapy in addition to local therapies and monitored for development of AICaP. A total of 211 men met eligibility criteria and PSA was 20ng/ml in 46%. Prostate biopsies indicated low grade disease in 38%, intermediate grade in 36%, and high grade in 25%. No NED was found by IHC in 54% when a cutoff of at least 30% positive staining was applied.

Tissue CgA expression directly correlated with Gleason score and tumor stage and was inversely correlated to serum PSA. AICaP developed in 112 men (53%) and 81 (38%) died of CaP. CgA staining in >30% of cancer cells on biopsy independently correlated with an increased risk of death in multivariate analysis. Supranormal serum levels of CgA were found in 23% at baseline, in 32% after one year, and in 32% after 2 years. Supranormal CgA at baseline significantly correlated with time to AICaP and overall survival.

The concordance between plasma CgA and tumor CgA positive staining was 60%, suggesting the need to assess expression by both means. This study suggests that CgA may be a useful biomarker to stratify patients for novel therapies.

Berruti A, Mosca A, Porpiglia F, Bollito E, Tucci M, Vana F, Cracco C, Torta M,
Russo L, Cappia S, Saini A, Angeli A, Papotti M, Scarpa RM, Dogliotti L

J Urol. ePub: July 16, 2007
DOI: 10.1016/j.juro.2007.05.018

Reported by UroToday Contributing Editor Christopher P. Evans, M.D

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