Ex vivo fluorescence confocal microscopy ensures representative tissue in prostate cancer biobanking: A feasibility study

Titze U, Sommerkamp J, Stege C, et al. Ex vivo fluorescence confocal microscopy ensures representative tissue in prostate cancer biobanking: A feasibility study. European Urology. 2023;83(Suppl. 1):S447-S448

Ex Vivo Fluorescence Confocal Microscopy (FCM) Ensures Representative Tissue in Prostate Cancer Biobanking: A Feasibility Study

Titze U, Sommerkamp J, Stege C, et al. Ex Vivo Fluorescence Confocal Microscopy (FCM) Ensures Representative Tissue in Prostate Cancer Biobanking: A Feasibility Study. International Journal of Molecular Sciences. 2022;23(20): 12103.Background: Biobanking of prostate carcinoma is particularly challenging due to the actual cancer within the organ often without clear margins. Frozen sections are to date the only way to examine the biobank material for its tumor content. We used ex vivo fluorescence confocal microscopy (FCM) to analyze biobank samples prior to cryoasservation. Methods: 127 punch biopsies were acquired from prostatectomy-specimens from 40 patients. These biopsies were analyzed with a Vivascope 2500-G4 prior to their transfer to the biobank. In difficult cases, larger samples of the prostatectomy specimens were FCM scanned in order to locate tumor foci. After patient acquisition, all samples were taken from the biobank and analyzed. We compared the results of the FCM examinations with the results of conventional histology and measured the DNA content. Results: With upstream FCM, the tumor content of biobank samples could be determined with high confidence. The detection rate of representative biobank samples was increased due to the rapid feedback. The biobank samples were suitable for further molecular analysis. Conclusion: FCM allows for the first time lossless microscopic analysis of biobank samples prior to their cryoasservation and guarantees representative tumor and normal tissue for further molecular analysis

PATZ1 fusions define a novel molecularly distinct neuroepithelial tumor entity with a broad histological spectrum

Large-scale molecular profiling studies in recent years have shown that central nervous system (CNS) tumors display a much greater heterogeneity in terms of molecularly distinct entities, cellular origins and genetic drivers than anticipated from histological assessment. DNA methylation profiling has emerged as a useful tool for robust tumor classification, providing new insights into these heterogeneous molecular classes. This is particularly true for rare CNS tumors with a broad morphological spectrum, which are not possible to assign as separate entities based on histological similarity alone. Here, we describe a molecularly distinct subset of predominantly pediatric CNS neoplasms (n = 60) that harbor PATZ1 fusions. The original histological diagnoses of these tumors covered a wide spectrum of tumor types and malignancy grades. While the single most common diagnosis was glioblastoma (GBM), clinical data of the PATZ1-fused tumors showed a better prognosis than typical GBM, despite frequent relapses. RNA sequencing revealed recurrent MN1:PATZ1 or EWSR1:PATZ1 fusions related to (often extensive) copy number variations on chromosome 22, where PATZ1 and the two fusion partners are located. These fusions have individually been reported in a number of glial/glioneuronal tumors, as well as extracranial sarcomas. We show here that they are more common than previously acknowledged, and together define a biologically distinct CNS tumor type with high expression of neural development markers such as PAX2, GATA2 and IGF2. Drug screening performed on the MN1:PATZ1 fusion-bearing KS-1 brain tumor cell line revealed preliminary candidates for further study. In summary, PATZ1 fusions define a molecular class of histologically polyphenotypic neuroepithelial tumors, which show an intermediate prognosis under current treatment regimens