PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens

Abstract

Background Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway “PEOPLE: PatiEnt prOstate samPLes for rEsearch” to collect high‐quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue. Methods Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset. Results Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture. Conclusion Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue.

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer

“…Matched tumour and benign human prostate tissue was collected from patients who had provided informed consent under UCL/UCLH Biobank ethics (REC 15/YH/0311), and sampled as per the PEOPLE method 27,42 . Tissue was cultured ex vivo and treated with AZD-1208, BEZ235, a combination of AZD-1208 and BEZ235, AUM302 or untreated, using the gelatin sponge method for 72 h 27 . Samples were used to create a tissue microarray and staining with H + E to assess morphology, as well as immunohistochemistry using Leica Biosystems BOND-MAX Automated IHC/ISH Stainer using antibodies Ki67 (Dako, M7240, 1:100, ER2 20 min), quantified for percentage positive nuclei using QuPath and cleaved Caspase 3 (Cell Signaling, 9664, 1:200, ER2 20 min), quantified by H-Score.…”

“…Matched tumour and benign human prostate tissue was collected from patients who had provided informed consent under UCL/UCLH Biobank ethics (REC 15/YH/0311), and sampled as per the PEOPLE method 27 , 42 . Tissue was cultured ex vivo and treated with AZD-1208, BEZ235, a combination of AZD-1208 and BEZ235, AUM302 or untreated, using the gelatin sponge method for 72 h 27 .…”

“…Human prostate tissue was cultured ex vivo following Magnetic Resonance Imaging (MRI) guided tumour targeting 27,28 . Four patients were recruited for this study, all of whom underwent radical prostatectomy and had Gleason ≥ 3 + 4, ≥ Likert 3 disease ( Supplementary Table S5).…”

Targeting the ERG oncogene with splice-switching oligonucleotides as a novel therapeutic strategy in prostate cancer

“…Tissue sampling from radical prostatectomy specimens was performed using the PEOPLE methodology 31 and ex vivo culture of tissue was performed as previously described 32 .…”

Use of Magnetic Resonance Imaging and Biopsy Data to Guide Sampling Procedures for Prostate Cancer Biobanking

“…This would improve the methodology in two ways; firstly, by reducing the number of tissue samples collected, increasing efficiency and reducing pressure on pathology departments and cost of storage, and secondly, by allowing fresh tissue to be used immediately without the need for immediate confirmation of tumor content, for new state of the art downstream technologies such as live tissue imaging, organoid generation or ex vivo culture. This research need has led to the development of the PEOPLE (PatiEnt prOstate samPLes for rEsearch) method, and the results from the first 84 cases biobanked using PEOPLE were recently published 8 . A variation of this method has also been published with a three-dimensional (3D) printed slicing apparatus and patient-specific mold, in order to facilitate ex vivo MRI on pre-and post-fixation tissue 9,10 .…”