Elizabeth A Punnoose1,6, Roberta Ferraldeschi2,3,6, Edith Szafer-Glusman1,6, Eric K Tucker4, Sankar Mohan5, Penelope Flohr3, Ruth Riisnaes3, Susana Miranda3, Ines Figueiredo3, Daniel Nava Rodrigues2, Aurelius Omlin2,3, Carmel Pezaro2,3, Jin Zhu1, Lukas Amler1, Premal Patel1, Yibing Yan1, Natalee Bales4, Shannon L Werner4, Jessica Louw4, Ajay Pandita5, Dena Marrinucci4, Gerhardt Attard3 and Johann de Bono3
PTEN gene loss occurs frequently in castration-resistant prostate cancer (CRPC) and may drive progression through activation of the PI3K/AKT pathway. Here, we developed a novel CTC-based assay to determine PTEN status and examined the correlation between PTEN status in CTCs and matched tumour tissue samples.
PTEN gene status in CTCs was evaluated on an enrichment-free platform (Epic Sciences) by fluorescence in situ hybridisation (FISH). PTEN status in archival and fresh tumour tissue was evaluated by FISH and immunohistochemistry.
Peripheral blood was collected from 76 patients. Matched archival and fresh cancer tissue was available for 48 patients. PTEN gene status detected in CTCs was concordant with PTEN status in matched fresh tissues and archival tissue in 32 of 38 patients (84%) and 24 of 39 patients (62%), respectively. CTC counts were prognostic (continuous, P=0.001). PTEN loss in CTCs associated with worse survival in univariate analysis (HR 2.05; 95% CI 1.17–3.62; P=0.01) and with high lactate dehydrogenase (LDH) in metastatic CRPC patients.
Our results illustrate the potential use of CTCs as a non-invasive, real-time liquid biopsy to determine PTEN gene status. The prognostic and predictive value of PTEN in CTCs warrants investigation in CRPC clinical trials of PI3K/AKT-targeted therapies.