Expression of tumour progression-associated genes in circulating tumour cells of patients at different stages of prostate cancer.
OBJECTIVE
To evaluate the presence of circulating tumour cells (CTCs) at different stages of prostate cancer using the AdnaTest® ProstateCancerDetect kit (Qiagen). Moreover, we aimed to assess the expression of transcripts that are specific for cancer stem cells (AdnaTest StemCell) and epithelial-mesenchymal transition (EMT) in CTCs (AdnaTest EMT), as well as additional genes that are known to promote prostate cancer progression.


PATIENTS AND METHODS
In this prospective study, we included 81 patients who underwent treatment for prostate cancer between 07/2014 and 02/2015, including: Group A, 18 patients (22.2%) with low-risk clinically localised prostate cancer; Group B, 25 patients (30.9%) with high-risk clinically localised prostate cancer; Group C, 11 patients (13.6%) with metastatic castration-sensitive prostate cancer (mCSPC); and Group D, 27 patients (33.3%) with metastatic castration-resistant prostate cancer (mCRPC). AdnaTest ProstateCancer and AdnaTest StemCell/EMT were performed in all cases. In addition, expression of the androgen receptor (AR), c-met, c-kit and thymidylate synthase (TYMS) in CTCs was assessed using specific polymerase chain reaction assays.


RESULTS
A positive AdnaTest ProstateCancer was present in three (16.7%), two (8.0%), six (54.5%) and 19 (70.5%) patients in groups A, B, C and D, respectively (P < 0.01, chi-squared test). The AdnaTest EMT and AdnaTest StemCell were positive in zero (0.0%), zero (0.0%), one (9.1%), and two (7.4%); and in five (27.8%), four (16.0%), three (27.3%), and 11 (40.7%) patients in groups A, B, C and D, respectively, with no significant differences noted between groups. CTCs expressing TYMS (44.4% and 50.0% vs 13.9%) or AR (18.2% and 25.9% vs 0.0%) were seen more commonly in patients in groups C and D vs patients with non-metastatic disease (all P < 0.05). Expression of c-kit and c-met were rare events, with only two patients positive for either marker.


CONCLUSIONS
AdnaTest ProstateCancerDetect exhibits positive results mainly in patients with metastatic disease. Expression of AR and TYMS are frequent events in CTCs of patients with advanced disease, whereas c-met and c-kit gene expression is seen in only a small proportion of patients. The implications of these results for the use of CTC analysis as a decision factor for personalised treatment strategies in advanced prostate cancer remain to be determined.
['Russo|Giorgio I|GI|0000-0003-4687-7353', 'Bier|Simone|S|', 'Hennenlotter|Jörg|J|', 'Beger|Gunthild|G|', 'Pavlenco|Lucretia|L|', 'van de Flierdt|Jens|J|', 'Hauch|Siegfried|S|', 'Maas|Moritz|M|', 'Walz|Simon|S|', 'Rausch|Steffen|S|', 'Bedke|Jens|J|', 'Morgia|Giuseppe|G|', 'Stenzl|Arnulf|A|', 'Todenhöfer|Tilman|T|0000-0002-8319-5602']
D000368:Aged D000369:Aged, 80 and over D015972:Gene Expression Regulation, Neoplastic D052138:Genes, Neoplasm D006801:Humans D008297:Male D008875:Middle Aged D009362:Neoplasm Metastasis D009360:Neoplastic Cells, Circulating D011446:Prospective Studies D064129:Prostatic Neoplasms, Castration-Resistant D019009:Proto-Oncogene Proteins c-kit D019859:Proto-Oncogene Proteins c-met
circulating tumour cells prostate cancer AdnaTest® stem cell #PCSM #ProstateCancer epithelial mesenchymal transition