A comprehensive study of circulating tumour cells at the moment of prostate cancer diagnosis: biological and clinical implications of EGFR, AR and SNPs

// Ignacio Puche-Sanz 1, * , Maria J. Alvarez-Cubero 2, * , Manrique Pascual-Geler 1 , Alba Rodriguez-Martinez 2, 6 , Miguel Delgado-Rodriguez 3 , Jose L. Garcia-Puche 2, 4 , Jose Exposito 4 , Inmaculada Robles-Fernandez 2 , Carmen Entrala-Bernal 5 , Jose A. Lorente 2, 6 , Jose M. Cozar-Olmo 1 and Maria J. Serrano 2, 4 1 Bio-Health Research Institute (Instituto de Investigacion Biosanitaria ibs.GRANADA), Complejo Hospitalario Universitario Granada (CHUG), Department of Urology, University of Granada, Granada, Spain 2 GENYO, Centre for Genomics and Oncological Research, Pfizer, University of Granada, Andalusian Regional Government, Granada, Spain 3 Division of Preventive Medicine and Public Health, CIBERESP, University of Jaen, Campus de las Lagunillas, Jaen, Spain 4 Bio-Health Research Institute (Instituto de Investigacion Biosanitaria ibs.GRANADA), Complejo Hospitalario Universitario Granada (CHUG), Department of Medical Oncology, University of Granada, Granada, Spain 5 Lorgen G.P., S.L., Business Innovation Center - BIC/CEEL, Technological Area of Health Science, Granada, Spain 6 Laboratory of Genetic Identification, Department of Legal Medicine, University of Granada, Granada, Spain * These authors have contributed equally to the work Correspondence to: Maria J. Serrano, email: mjose.serrano@genyo.es Keywords: prostate cancer, circulating tumor cells, androgen receptor, epidermal growth factor receptor, single nucleotide polymorphisms Received: August 12, 2016     Accepted: June 02, 2017     Published: July 31, 2017 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.