Login to Access Video or Poster Abstract: MP87-06
Sources of Funding: Qiagen GmbH Germany

Introduction

Different platforms exist for the detection of circulating tumor cells (CTC). The identification of the androgen-receptor variant 7 (AR-V7) as a predictor of drug resistance has shown that the Adnatest® is a promising platform for analysis of prostate cancer (PC) associated mRNAs in CTC. Although it has been recently reported that the Adnatest® shows higher CTC detection rates compared to the CellSearch&[copy] platform in patients with metastatic castration resistant PC (mCRPC) (Danila et al. 2016), there is only limited data on stage-dependant prevalence of CTC using this platform. Moreover, the ability of this platform to analyze disease-relevant transcripts beyond AR-V7 has not been assessed sufficiently yet. The aim of the present study was to evaluate the presence of CTC detected by the Adnatest® in different stages of PC. Moreover, we assessed the expression of transcripts specific for cancer stem cells and epithelial mesenchymal transition (EMT) in CTC and further genes that are known to promote PC progression.

Methods

In this prospective study, we included 42 patients with clinically localized PC (17 low risk, 25 high risk) and 38 patients with metastatic PC (11 patients with metastatic castration sensitive PC (mCSPC) and 27 with mCRPC) between 07/2014 and 02/2015. CTC were enriched using the Adnatest® System (Qiagen, Hilden, Germany). Presence of CTC was assessed using the Adnatest® ProstateCancerDetect which quantifies the expression of PSA, PSMA and EGFR mRNA in CTC. Moreover, CTC with stem cell or EMT-like phenotypes were analyzed using the Adnatest® StemCell/EMT kit. Expression of the androgen receptor (AR), c-met, c-kit and thymidylate synthase (TYMS) were assessed using specific polymerase chain reaction (PCR) assays. Results were correlated with clinical data.

Results

The Adnatest® ProstateCancerDetect was positive in 8.0%, 18.8%, 54.6% and 70.4% of patients with low risk cM0 PC, high risk cM0 PC, mCSPC and mCRPC (p<0.001). CTCs with stem cell or EMT-features were found in 36.8% and 7.9% of cM1 patients vs. 20.9% and 0% of patients with cM0 disease (p=0.1 and 0.06). C-kit or c-met expressing CTC were present in only one (2.8%) and two patients (5.4%) with cM1 disease. TYMS positive CTCs were present in 7.1%, 20.8%, 48.1% and 50% of patients with low risk cM0 PC, high risk cM0 PC, mCSPC and mCRPC (p=0.01) whereas AR-positive CTCs were found in 0%, 0%, 27.3% and 44.4% of patients (p<0.001).

Conclusions

The presence of CTCs expressing PC-associated transcripts detected by the Adnatest® shows a clear correlation with clinical stage. AR and TYMS expression are frequently detected in CTC of patients with metastatic PC, whereas c-kit or c-met expressing CTC are rare events in PC patients. The potential prognostic and predictive impact of gene expression profiles of CTC detected by the Adnatest® is currently under investigation.

Funding

Qiagen GmbH Germany