Transcriptomic Features of Cribriform and Intraductal Carcinoma of the Prostate.

Cribriform (CF) and/or intraductal carcinoma (IDC) are associated with more aggressive prostate cancer (CaP) and worse outcomes.

The transcriptomic features that typify CF/IDC are not well described and the capacity for clinically utilized genomic classifiers to improve risk modeling for CF/IDC remains undefined.

We performed a retrospective review of CaP patients who had Decipher testing at a single high-volume institution. Index lesions from radical prostatectomy specimens were identified by genitourinary pathologists who simultaneously reviewed prostatectomy specimens for the presence of CF and IDC features. Patients were grouped based on pathologic features, specifically the absence of CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+).

Clinical, pathologic, and genomic categorical variables were assessed using the Pearson chi-square test, while quantitative variables were assessed with the Kruskal-Wallis test. Multivariable logistic regression was used to identify the predictors of high-risk Decipher scores (>0.60). A gene set enrichment analysis was performed to identify genes and gene networks associated with CF/IDC status.

A total of 463 patients were included. Patients who were CF+/IDC+ had the highest Decipher risk scores (CF+/IDC+: 0.79 vs CF+/IDC-: 0.71 vs CF-/IDC-: 0.56, p < 0.001). On multivariate logistic regression, predictors of high-risk Decipher scores included the presence of CF, both alone (CF+/IDC-; odds ratio [OR]: 5.45, p < 0.001) or in combination with positive IDC status (CF+/IDC+; OR: 6.87, p < 0.001). On the gene set enrichment analysis, MYC pathway upregulation was significantly enriched in tumor samples from CF/IDC-positive patients (normalized enrichment score [NES]: 1.65, p = 0.046). Other enriched pathways included E2F targets (NES: 1.69, p = 0.031) and oxidative phosphorylation (NES: 1.68, =0 .033).

This is the largest series identifying an association between a clinically validated genomic classifier and the presence of CF and IDC at radical prostatectomy. Tumors with CF and intraductal features were associated with aggressive transcriptomic signatures.

Genomic-based tests are becoming readily available for the management of prostate cancer. We observed that Decipher, a commonly used genomic test in prostate cancer, correlates with unfavorable features in tissue specimens.

European urology focus. 2022 May 31 [Epub ahead of print]

Zaeem Lone, Tarik Benidir, Magdalena Rainey, Monica Nair, Elai Davicioni, Ewan A Gibb, Sean Williamson, Shilpa Gupta, Moshe Chaim Ornstein, Rahul Tendulkar, Christopher Weight, Jane K Nguyen, Eric A Klein, Omar Y Mian

Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA. Electronic address: ., Glickman Urological and Kidney Institute, Cleveland Clinic, Cleveland, OH, USA., Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA., Decipher Biosciences, San Diego, CA, USA., Cleveland Clinic Department of Pathology, Cleveland, OH, USA., Cleveland Clinic Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA., Cleveland Clinic Lerner College of Medicine, Cleveland, OH, USA; Cleveland Clinic Taussig Cancer Center, Cleveland Clinic, Cleveland, OH, USA. Electronic address: .

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