Background: Although extensive research highlights the detrimental effect of cribriform pattern 4 (CP4) on survival in non-high-risk prostate cancer (PC), its prognostic significance in high-risk PC is not well understood. Methods: The individual patient data from the The Cancer Genome Atlas (TCGA) database following radical prostatectomy was retrospectively examined. A predefined statistical analysis was conducted to evaluate the potential association between CP4 and progression-free survival (PFS). Results: Of the 135 patients examined, CP4 was present in 66 (48.9%). Median follow-up was 45.93 months (interquartile range: 22.87, 80.10). Cribriform pattern 4 was associated with a significantly reduced PFS (subdistribution hazard ratio, 1.99; 95% CI, 1.01-3.92; P = .045) following adjustment for covariates. Conclusions: The presence of CP4 in high-risk Gleason 8-10 PC portends worse PFS. Further studies are warranted to fully understand its implications in risk stratification and post-operative management of PC. Cite this article as: Walburn T, Tuac Y, Aktan C, et al. Impact of cribriform pattern on progression-free survival after radical prostatectomy in gleason score 8-10 prostate cancer. Eurasian J Med. 2025; 57(1), 0804 doi: 10.5152/eurasianjmed.2025.25804.

Background: Prostate cancer is a common malignancy among men worldwide, with various histopathologic features that influence its progression and prognosis. One such feature is perineural invasion (PNI), which has been associated with aggressive disease. In this retrospective study, we analyzed genomic alterations associated with PNI in patients who underwent radical prostatectomy. Methods: A total of 421 prostate cancer patients who underwent radical prostatectomy without neoadjuvant therapy were identified from The Cancer Genome Atlas. PNI was present in 378 patients (89.8%) and absent in 43 (10.2%). Differentially expressed genes were identified, and mRNA expression levels of key genes were analyzed. The prognostic significance of these genes was evaluated using log-rank tests and Cox proportional hazards models to estimate hazard ratios and 95% confidence intervals. Results: Levels of COL9A3, ASPN, ESR1, MUC1, PIP, SFRP4, KRT19, CLDN1, and COMP were significantly higher in the tumor tissues of patients in the PNI group compared to those in the non-PNI group (q < 0.05), and RYR2, MME, and AZGP1 expression levels were significantly higher in the non-PNI group (q < 0.05). A high mRNA expression level of AZGP1 was associated with longer disease-free survival, whereas high mRNA expressions of ASPN, COMP, RYR2, and SFRP4 were associated with shorter disease-free survival. Conclusions: Prostate cancer patients with genomic alterations associated with PNI may face a higher risk of disease progression after prostatectomy, highlighting the need for further prospective studies to validate these findings.

Background/Objectives: Cribriform architecture is an adverse histopathologic feature in prostate cancer and has been associated with poor oncologic outcomes. Emerging evidence suggests that cribriform-positive tumors may behave as a biologically non-localized disease, raising the possibility of early occult dissemination. Lymphovascular invasion (LVI) is a key pathological marker of metastatic potential, but its relationship with cribriform architecture has not been evaluated. We examined the association between cribriform morphology and LVI to provide biological context for the aggressive clinical course of cribriform-positive prostate cancer. Methods: We performed a retrospective analysis of patients with prostate adenocarcinoma who underwent radical prostatectomy and had available clinicopathologic data. Cribriform architecture was determined by a centralized pathology review, and LVI status was obtained from original pathology reports. Unadjusted associations were evaluated using contingency tables. Multivariable logistic regression was used to assess whether cribriform architecture was independently associated with LVI after adjustments for Gleason score, tumor stage, and nodal status. Results: Among 338 patients, 28 (8.3%) had LVI and 123 (36.4%) had cribriform architecture. LVI was more common in cribriform-positive than cribriform-negative tumors (17.9% vs. 2.8%; p < 0.001), corresponding to a crude odds ratio (OR) of 7.6 (95% CI, 3.0–19.3). Cribriform architecture remained independently associated with LVI after adjustment (adjusted OR, 5.20; 95% CI, 2.12–1.40; p < 0.001). Conclusions: Cribriform architecture is strongly and independently associated with LVI, supporting a biological link between cribriform morphology and early metastatic dissemination. These findings support the design of prospective, biomarker-driven studies to evaluate treatment intensification strategies in this high-risk subgroup.

Background/Objectives: Cribriform architecture is an adverse Gleason pattern 4 morphology associated with aggressive prostate cancer outcomes. Tertiary Gleason pattern 5, even as a minor component, may also identify tumors with higher-grade biology not fully captured by conventional Grade Group assignment. We examined whether cribriform architecture is associated with tertiary Gleason pattern 5 in patients undergoing radical prostatectomy. Methods: We performed a retrospective cross-sectional study of radical prostatectomy specimens from patients with prostate adenocarcinoma who underwent radical prostatectomy and had available clinicopathologic data. A centralized pathology review of digitized radical prostatectomy slides was used to assess cribriform architecture. Tertiary Gleason pattern 5 status was obtained from original pathology reports. Multivariable logistic regression was used to evaluate the association between cribriform architecture and tertiary Gleason pattern 5 after adjustment for age, preoperative prostate-specific antigen level, prostatectomy Gleason score, pathologic tumor stage, and margin status. Results: Among 303 patients, 47 (15.5%) had tertiary Gleason pattern 5. Cribriform architecture was more common in tumors with tertiary Gleason pattern 5 than in those without (70% vs. 21%; p < 0.001). On multivariable analysis, cribriform architecture remained independently associated with tertiary Gleason pattern 5 (adjusted odds ratio of 9.46; 95% confidence interval of 4.49–21.0; p < 0.001). The model demonstrated good discrimination, with an area under the receiver operating characteristic curve of 0.80. Conclusions: Cribriform architecture was strongly associated with tertiary Gleason pattern 5. These findings suggest that cribriform-positive tumors may be more likely to harbor minor high-grade pattern 5 components.

Lymphovascular invasion is an adverse pathologic feature in prostate cancer, but its independent molecular drivers remain unclear due to strong confounding by tumor grade and stage. We performed a confounder-adjusted transcriptomic analysis of 403 TCGA-PRAD samples. Differential expression was adjusted for Gleason score and pathological T stage. A transcriptional profile associated with LVI was derived and tested in multivariable logistic and Cox proportional hazards models for biochemical recurrence-free survival, with bootstrap internal validation. After multivariable adjustment, 129 genes were independently associated with LVI. This gene set was overwhelmingly enriched for interferon-alpha/beta signaling and antiviral response pathways. A continuous composite score derived from this profile predicted a reduced risk of biochemical recurrence independently of standard clinicopathological factors (adjusted HR per unit = 0.911, 95% CI: 0.835–0.993, p = 0.033). Multi-omics integration revealed subtle promoter hypomethylation and strong correlations between methylation and expression for key interferon genes, supporting transcriptional regulation. We identify a robust, interferon-response transcriptional profile that specifically defines LVI in prostate cancer after accounting for major clinical confounders. This transcriptional signature provides independent prognostic information, refines the biological understanding of LVI, and presents a novel targetable pathway for further investigation.