Carcinome intracanalaire de la prostate

Lab Invest. 2026 Jul 17:106154. doi: 10.1016/j.labinv.2026.106154. Online ahead of print.ABSTRACTPURPOSE: Cribriform (Crib) acinar adenocarcinoma (AAC), intraductal carcinoma of the prostate (IDC-P), atypical intraductal proliferation (AIP) and ductal adenocarcinoma (DAC) are linked to poor outcomes in prostate cancer (PCa). We analyzed their gene expression using spatial transcriptomics.MATERIALS AND METHODS: A tissue microarray of 18 FFPE cores from 17 prostatectomies was profiled for expression of 18,676 mRNAs with the Bruker GeoMx Digital Spatial Profiler platform. 53 areas of interest were selected based on H&E, PIN4 IHC and fluorescence markers. Gene set enrichment analysis was conducted for Reactome gene sets.RESULTS: Most patients had grade group ≥3 (94%) and ≥pT3 disease (65%). At a median follow-up of 47 months (range, 18-130), 31% developed metastases. 16 tumors showed mixed morphology. 3 DACs had adjacent intraductal components with preserved basal cells (ductal IDC-P). 9/10 acinar IDC-P and 6/7 AIP presumably represented intraductal spread (invasive type); one was mostly non-invasive (95% IDC-P/AIP, putative precursor type). Crib AAC, acinar IDC-P, and AIP demonstrated substantial transcriptomic similarity, with only 4 differentially expressed genes between acinar IDC-P and crib AAC and between acinar IDC-P and AIP. Crib AAC exhibited Notch signaling and homologous recombination DNA repair enrichment versus low-grade AAC. Acinar IDC-P upregulated GADD45G/ERRFI1 and downregulated CCN3/TMEFF2, with reduced PKN1-mediated androgen receptor signaling versus crib AAC. AIP showed reduced GPCR signaling versus IDC-P and crib AAC. Acinar IDC-P upregulated TSPAN8/CA4, and downregulated TRPM8/DHCR24 versus AIP. Putative precursor-type IDC-P/AIP downregulated oncogenic and stemness programs versus invasive type. DAC was transcriptomically more similar to crib AAC than to non-crib AAC. Ductal IDC-P downregulated luminal epithelial programs, and upregulated antigen presentation/immune signaling versus DAC.CONCLUSIONS: Crib AAC, acinar IDC-P, and AIP demonstrated substantial transcriptomic similarity despite distinct differences. DAC showed greater transcriptomic similarity to crib AAC than to non-crib AAC.PMID:42468875 | DOI:10.1016/j.labinv.2026.106154

Prostate Cancer Prostatic Dis. 2026 Aug 3. doi: 10.1038/s41391-026-01143-2. Online ahead of print.ABSTRACTBACKGROUND: Cribriform pattern (CP) and intraductal carcinoma of the prostate (IDC-P) are recognised as adverse histopathological markers. However, their precise prognostic weight in the post-radical prostatectomy (RP) setting remains poorly standardised. We performed a systematic review and meta-analysis to quantify the association between CP/IDC-P and biochemical recurrence (BCR).METHODS: A systematic search of MEDLINE, Scopus, and Web of Science was conducted for studies published from 2016 onwards, coinciding with the 2016 WHO and subsequent ISUP consensus recommendations. The primary endpoint was BCR. Hazard ratios (HR) were synthesised using random-effects models with restricted maximum likelihood (REML) estimation.RESULTS: Eight retrospective studies were eligible for quantitative synthesis. The cumulative prevalence of CP/IDC-P was 27%. On univariable analysis, CP/IDC-P was significantly associated with BCR (HR: 2.76; 95% CI: 2.23-3.41). This association remained robust in multivariable models adjusting for pathological stage and Grade Group (HR: 2.59; 95% CI: 1.44-4.67) and CAPRA-based preoperative frameworks (HR: 1.78; 95% CI: 1.03-3.08). Isolated CP demonstrated a more stable prognostic signal (HR: 3.16) compared to IDC-P (HR: 4.24), the latter being characterised by wider prediction intervals. The main limitations include the retrospective nature of primary studies and the inherent risk of confounding.CONCLUSIONS: CP and IDC-P are potent, independent predictors of BCR following RP. These findings support the mandatory reporting of such architectures according to ISUP standards and their integration into contemporary post-surgical risk-stratification algorithms to optimise follow-up and adjuvant therapy selection.PMID:42547539 | DOI:10.1038/s41391-026-01143-2

Urol Oncol. 2026 Aug 7:S1078-1439(26)00608-3. doi: 10.1016/j.urolonc.2026.07.008. Online ahead of print.ABSTRACTINTRODUCTION: Current risk stratification after radical prostatectomy (RP) relies on Grade Group (GG) and genomics, which may not fully capture metastatic potential. Unfavorable histology (UH), defined by adverse architectural patterns such as large cribriform carcinoma and intraductal carcinoma, has emerged as a strong predictor. We evaluated whether integrating genomic and other clinicopathologic variables improves prediction beyond quantitative UH burden.METHODS: We analyzed 418 men from an event-enriched RP cohort (1987-2004) with centralized pathology review, Genomic Prostate Score (GPS), and long-term follow-up. We recorded the percentage of tumor with UH (UH%), cribriform size, GG, stage, margin status, prostate-specific antigen, and GPS. Multivariable Cox models and a sequential modeling framework evaluated independent associations and incremental predictive performance for metastasis at 15 years.RESULTS: During median 15.5-year follow-up, 102 men (24%) developed metastases, all within UH-positive tumors. UH ≥10% was strongly associated with metastasis (hazard ratios [HR] 50.95, 95% confidence intervals [CI] 10.4-249). GPS (HR 1.03 per unit, 95% CI 1.01-1.05) and cribriform size (HR 1.0007 per μm, 95% CI 1.0003-1.0010) were independently associated but added only modest discrimination. UH% alone achieved high 15-year discrimination (c-index ∼0.85); inclusion of GPS and cribriform size increased this to 0.901. Limitations include retrospective design and single-institution pathology review.CONCLUSION: UH% is the dominant determinant of metastatic risk after RP, offering greater prognostic discrimination than GG, stage, and other clinicopathologic variables. Genomic classifiers and cribriform size provide secondary refinement but do not materially alter risk once UH burden is established. These findings support pathology-anchored risk models.PMID:42567796 | DOI:10.1016/j.urolonc.2026.07.008