Abstract
Circulating tumor cells (CTCs) have been recently accepted as prognostic markers in metastatic prostate cancer (PCa). However, very few studies have analyzed their role in early-stage PCa. The aim of this research is to study the value of CTCs at the moment of PCa diagnosis and to identify different subpopulations of CTCs. Patients with PSA value > 4 ng/ml and clinical suspicion of PCa were included. Samples were collected immediately before prostatic biopsy. CTCs were isolated by immunomagnetic technique using a multi-CK specific antibody. Molecular expression of EGFR and AR in the tissue was analysed by real-time PCR. Up to eight different SNPs in patients’ blood DNA were studied.In a total of 86 patients, the CTC detection rate was 18.6%. The sensitivity, specificity, positive and negative predictive values of CTCs to detect PCa was 14.2%, 78.4%, 31.2% and 57.4%, respectively. Up to 75% of CTC-positive patients were AR-negative. A direct association was found between the expression of AR in the prostatic tissue and the presence of CTCs in blood (p<0.05). We observed an inverse relation between the expression of EGFR in the tissue and the expression of AR in the CTCs. No significant association between SNPs and CTCs was found.The low detection rate of CTCs in early-stage PCa limits their role as a diagnostic marker. Nevertheless, we show that they may hide important prognostic information. Overexpression of AR in the prostate may facilitate cell dissemination.
Highlights
Prostate cancer (PCa) is the most frequent noncutaneous cancer affecting men and the second leading cause of cancer-specific mortality in males in the Western world [1]
In 2008, De Bono et al [3] reported, in a multicentre prospective study, that circulating tumour cells (CTCs) counting was an independent predictor of overall survival (OS) in patients with metastatic castration-resistant prostate cancer
No significant association was found between Circulating tumor cells (CTCs) status and the other clinical characteristics, including prostate volume, tPSA, fPSA, fPSA/tPSA or testosterone levels
Summary
Prostate cancer (PCa) is the most frequent noncutaneous cancer affecting men and the second leading cause of cancer-specific mortality in males in the Western world [1]. Given the potential serious side effects associated with PCa treatment, along with concerns about overdiagnosis, there is an urgent need for the discovery of biomarkers to obtain better predictive and prognostic information at the moment of diagnosis [2]. For this purpose, an optimal knowledge of PCa molecular biology is needed. Numerous studies have demonstrated the prognostic and predictive ability of CTCs in metastatic PCa patients. Only a few have analysed their role in localised PCa patients, mainly due to the very low counting rates in non-metastatic stages [4,5,6,7]. Adequate characterisation or phenotyping of CTCs, based on current knowledge of PCa biology, may be the key to overcoming this problem [8]
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