However, AS is widely considered unsuitable for patients with intraductal or cribriform patterns identified in biopsy. Additionally, focal therapy is emerging as a promising treatment alternative, particularly for patients with Grade Group 3 prostate cancer (Gleason 4+3); however, most trials exclude patients with cribriform and intraductal carcinoma on biopsy.
The problem lies, however, in the limited sensitivity (less than 50%) of prostate biopsy to detect these aggressive features.3 Furthermore, false negative biopsies for intraductal carcinoma/cribriform pattern were independently associated with biochemical recurrence and adverse pathology at radical prostatectomy.4
Thus, there is an unmet need for biomarkers capable of detecting intraductal and cribriform patterns. Extracellular vesicles contain various biomolecules, including proteins, lipids, DNA, and RNA, reflecting the molecular composition of their tissue of origin and showing tremendous potential as prostate cancer biomarkers.5
In this study, urinary extracellular vesicle (EV) protein signatures were profiled to explore potential biomarkers for detecting cribriform and intraductal carcinoma patterns in prostate cancer.6 We identified 171 differentially expressed proteins between intraductal carcinoma/cribriform and non-intraductal/non-cribriform cases. Notably, two proteins, S100A10 and PTGES3, remained significantly dysregulated even after adjusting for Gleason grade, indicating their potential as biomarkers. Additionally, TMBIM1 (Bax Inhibitor-1), which plays a crucial role in regulating apoptosis and is overexpressed in aggressive prostate cancer, was found to be upregulated in IDC/cribriform cases, reinforcing its association with poor prognosis. Proteins involved in androgen response were also generally downregulated in IDC/cribriform cases, suggesting an association with these aggressive patterns. The findings underscore the diagnostic potential of urinary EVs as a non-invasive source for identifying biomarkers specific to intraductal and cribriform prostate cancer, addressing the current limitations in biopsy sensitivity.
Written by: Rui M. Bernardino, MD,1,2 Ana Sofia Carvalho,2 Neil Fleshner,1 Rune Matthiesen2
- Division of Urology, Department of Surgical Oncology, University of Toronto, Princess Margaret Cancer Centre, Toronto, ON
- Computational and Experimental Biology Group, NOVA Medical School, Faculdade de Ciências Médicas, Universidade NOVA de Lisboa, Portugal
- Bernardino R, Sayyid RK, Leão R, Zlotta AR, van der Kwast T, Klotz L, et al. Increasing trend of utilising active surveillance for Gleason Score 7 (3 + 4) prostate cancer. BJU Int [Internet]. 2023 Dec 1 [cited 2024 Jan 4];132(6).
- Bernardino R, Sayyid RK, Leão R, Zlotta AR, Kwast T van der, Klotz L, et al. Using active surveillance for Gleason 7 (3+4) prostate cancer: A narrative review. Canadian Urological Association Journal [Internet]. 2023 Dec 21 [cited 2024 Jan 4];18(4).
- Bernardino RM, Sayyid RK, Lajkosz K, Al-Daqqaq Z, Cockburn JG, Chavarriaga J, et al. Limitations of Prostate Biopsy in Detection of Cribriform and Intraductal Prostate Cancer. Eur Urol Focus [Internet]. 2023 Sep [cited 2023 Sep 24]
- Bernardino RM, Yin LB, Lajkosz K, Cockburn JG, Wettstein M, Sayyid RK, et al. Undetected Cribriform and Intraductal Prostate Cancer at biopsy is associated with adverse outcomes. Prostate Cancer Prostatic Dis [Internet]. 2024 [cited 2024 Nov 3]
- Bernardino RMM, Leão R, Henrique R, Pinheiro LC, Kumar P, Suravajhala P, et al. Extracellular Vesicle Proteome in Prostate Cancer: A Comparative Analysis of Mass Spectrometry Studies. Int J Mol Sci [Internet]. 2021 Dec 1 [cited 2023 May 12];22(24).
- Bernardino R, Carvalho AS, Hall MJ, Alves L, Leão R, Sayyid R, et al. Profiling of urinary extracellular vesicle protein signatures from patients with cribriform and intraductal prostate carcinoma in a cross-sectional study. Sci Rep [Internet]. 2024 Dec 1 [cited 2024 Nov 3];14(1).