Abstract 6617: Gleason score 6 often coexists with Gleason score 7 adenocarcinoma within 3D z-levels of a prostate biopsy
Authors: Farré Xavier , Roybal Vanessa , Koyuncu Can , Chow Sarah , Huang Hongyi , Aberdeen Alan , Janowczyk Andrew , Madabhushi Anant , True Lawrence D. , Liu Jonathan T. 
Published: June 2023

Abstract
Background: Primary prostate cancer is diagnosed by biopsy. However, biopsies sample only a limited amount of the prostate gland. Many studies report that GS6 cancer at biopsy is often upgraded in the radical prostatectomy. Undergrading results from sampling limitations of the biopsy - both of the prostate and of tissue within the biopsy. Since pathological diagnosis is based on 4 micron thick sections of 1 mm thick biopsies, only 0.4% of the biopsy is analyzed. We hypothesize that the evaluation of a biopsy in 3D results in variable Gleason scores or even no cancer in certain z-levels. Here, we examined 3D pathology image datasets of Gleason score 7 (GS7) biopsies using a web-based image viewing platform to determine if they underdiagnose and/or undergrade cancer when examined by conventional 2D slide-based histology.
Methods: We used a custom-developed 3D open-top light-sheet (OTLS) microscope, not yet available for clinical use, to study all z-levels of a prostate biopsy. The patient cohort used in this study came from the Canary TMA study. 105 prostate biopsies were non-destructively digitized in 3D with at least 500 z-levels per biopsy (at a spacing of ~1 micron per level). Samples were stained with fluorescence analogs of H&E. The image datasets were false colored to mímic conventional H&E histology. A pathologist reviewed the images using a web-based image platform and gave overall Gleason scores (OGS) based examing all z-levels within a biopsy. Six z-levels (1, 100, 200, 300, 400 and 500) were selected for 2D Gleason scoring.
Results: 63 images had a OGS of 3+4 and 42 a OGS 4+3. We found presence of GS6 (Gleason grade 3 glands only) in some z-levels: 32 cases (50.8%) with OGS 3+4 and 4 cases (9.5%) with OGS 4+3. When we only studied the 6 selected z-levels, we found z-levels with no cancer in 4 cases (6.3%) of OGS 3+4 and 2 cases (4.8%) in OGS 4+3. In addition, we found z-levels with limited number of glands. We reported these levels as Atypical Small Acinar Proliferation (ASAP) in 2 cases (3.2%) with OGS 3+4 and 3 cases (7.1%) with OGS 4+3. Examining all z-levels enabled unambiguous grading of biopies containing z-levels with ASAP and tangential sections.
Conclusion: We describe the frequent coexistence of GS6 z-levels within a OGS7 3D prostate biopsy. This finding supports prior observations that finding of GS6 prostate cancer in a 2D-based sections of prostate cancer does not rule out a higher Gleason grade areas in other parts of the prostate nor in other levels of each biopsy. We also show that availability of 3D levels eases the interpretation of ASAP glands and tangential sections.
Citation Format: Xavier Farré, Vanessa Roybal, Can Koyuncu, Sarah Chow, Hongyi Huang, Alan Aberdeen, Andrew Janowczyk, Anant Madabhushi, Lawrence D. True, Jonathan T. Liu. Gleason score 6 often coexists with Gleason score 7 adenocarcinoma within 3D z-levels of a prostate biopsy [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 6617.