PTEN loss in circulating tumour cells correlates with PTEN loss in fresh tumour tissue from castration-resistant prostate cancer patients
| Autor: | Ines Figueiredo, Natalee Bales, Daniel Nava Rodrigues, Lukas C. Amler, Ruth Riisnaes, Yibing Yan, Sankar Mohan, Edith Szafer-Glusman, Aurelius Omlin, Gerhardt Attard, Dena Marrinucci, Eric Tucker, Elizabeth Punnoose, Roberta Ferraldeschi, Carmel Pezaro, Shannon L. Werner, Penelope Flohr, Jin Zhu, Johann S. de Bono, Premal Patel, Jessica Louw, Ajay Pandita, Susana Miranda |
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| Rok vydání: | 2015 |
| Předmět: |
Male
Oncology PTEN Cancer Research medicine.medical_specialty Colorectal cancer Phosphatidylinositol 3-Kinases Prostate cancer Breast cancer FISH abiraterone Internal medicine medicine Humans Liquid biopsy Molecular Diagnostics In Situ Hybridization Fluorescence PI3K/AKT/mTOR pathway Aged L-Lactate Dehydrogenase biology business.industry PTEN Phosphohydrolase Cancer prostate cancer Neoplastic Cells Circulating Prognosis medicine.disease Immunohistochemistry Prostatic Neoplasms Castration-Resistant Disease Progression biology.protein Cancer biomarkers CTCs business |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| Popis: | Background: 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. Methods: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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