Circulating tumor cell (CTC) detection, N-terminal androgen (AR) characterization, and PTEN loss in metastatic or advanced castration resistant prostate cancer (CRPC)
| Autor: | Premal Patel, Jane Petersen, Dena Marrinucci, Ling Huw, Shidong Jia, Shannon L. Werner, Amanda K. L. Anderson, Sarah Baird |
|---|---|
| Rok vydání: | 2016 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty biology business.industry medicine.drug_class Castration resistant medicine.disease Androgen Patient response Ipatasertib Prostate cancer chemistry.chemical_compound Circulating tumor cell Oncology chemistry medicine Cancer research biology.protein PTEN DAPI business |
| Zdroj: | Journal of Clinical Oncology. 34:195-195 |
| ISSN: | 1527-7755 0732-183X |
| DOI: | 10.1200/jco.2016.34.2_suppl.195 |
| Popis: | 195 Background: Detection and characterization of CTCs offers a minimally invasive mechanism for understanding patient response to therapy and disease evolution. Here we describe a proprietary technology platform to examine CTC incidence, N-terminal AR expression, and PTEN loss in metastatic or advanced CRPC patient samples from a phase II clinical trial (GO27983) testing the combination of the AKT inhibitor ipatasertib and abiraterone. Methods: Blood samples from CRPC patients (n = 283) were collected at screening and shipped to Epic Sciences. Upon receipt, the nucleated cells were plated onto microscope slides and stored at -80C. Two slides were thawed per patient and analyzed with an N-terminal AR CTC assay. CTCs were detected using a combination of CD45 exclusion, CK and N-terminal AR expression, and morphologic criteria. Traditional (CD45-, CK+, DAPI+) and Non-Traditional (CD45-/CK- with distinct morphology or CD45-/CK+ with fragmented nuclei) CTCs were enumerated and N-terminal AR expression was quantified for each CTC. Samples with > 2 Traditional CTCs enumerated per slide were further evaluated for PTEN loss by FISH (n = 170). Results: Traditional CTCs were detected ( ≥ 1 cell/ml) in 86% (242 of 283) of samples. Non-traditional CTCs were detected in 93% (263 of 283) of patients. N-terminal AR positivity was detected ( ≥ 1 AR+ cell/ml) in 53% (128 of 242) of Traditional CTC-positive samples, with the % positivity ranging from 0.4-100%. PTEN status was determined for 66% (160 of 243) of patients with Traditional CTCs detected. Patients with homozygous (HO) PTEN loss had a significantly higher mean CTC/mL (p = 0.0013) and AR+ CTC/mL value (p = 0.0014) than patients with PTEN non-deleted status. Conclusions: The ability of the Epic Sciences platform to detect AR+ CTCs and PTEN loss at screening provides a non-invasive approach to characterizing and monitoring CTCs identified in advanced CRPC patients. The study is ongoing to monitor longitudinal changes in CTC incidence and AR expression in relation to PTEN status. Clinical trial information: NCT01485861. |
| Databáze: | OpenAIRE |
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