Lone, Z., Benidir, T., Rainey, M., Nair, M., Davicioni, E., Gibb, E., Williamson, S., Nguyen, J.K., Gupta, S., Ornstein, M.C., Ciezki, J.P., Stephans, K.L., Tendulkar, R.D., Weight, C., Klein, E.A., and Mian, O.Y.
Morphologic features such as cribriform and intraductal carcinoma (CF/IDC) are associated with unfavorable oncologic outcomes in prostate cancer (PCa) patients. Few studies have investigated whether commonly utilized genomic classifiers such as Decipher are associated with CF and/or IDC. The objective of our study was to identify any correlations between Decipher genomic risk score and CF/IDC status while also assessing PCa transcriptomic features of these pathologic features. A retrospective review of PCa patients who had Decipher testing at a single high-volume center between 2009-2020 was performed. A genitourinary pathologist reviewed specimens for the presence of CF and IDC features and annotated three groups: absent CF/IDC (CF-/IDC-), CF positive only (CF+/IDC-), and CF/IDC positive (CF+/IDC+). Categorical clinical, genomic, and pathologic variables were assessed using the Pearson Chi-Square test, quantitative with the Kruskal-Wallis test. Molecular subtyping using the PAM50 classifier was performed. Gene set enrichment analysis (GSEA) was performed to identify differentially expressed pathways between patients that were CF-/IDC- compared to CF+/IDC+. Four hundred and sixty-three patients were included. Patients that were CF+/IDC+ had the highest mean Decipher scores (CF+/IDC+: 0.77 vs. CF+/IDC-: 0.71 vs. CF-/IDC-: 0.61, p<0.001). Patients who were CF+/IDC also had the highest rates of Grade Group ≥ 3 disease on final pathology (CF+/IDC+: 79% vs. CF+/IDC-: 52% vs. CF-/IDC-: 52%, p<0.001). Gene network level transcriptomic analysis revealed upregulation of MYC pathway genes (Normalized Enrichment Score (NES): 1.65, p=0.04) and E2F targets (NES: 1.69, p=0.03) respectively. Molecular subtyping revealed that CF+/IDC+ tumors were associated with luminal proliferating type B classification (CF+/IDC+: 53% vs. CF+/IDC-: 48% vs. CF-/IDC-: 29%, p<0.001). We report an association between Decipher score and Cribriform/Intraductal morphology in PCa. CF+/IDC+ tumors had higher average Decipher scores and upregulated adverse gene programs (e.g., MYC, pRB1). CF+/IDC+ was associated with the luminal proliferating B subtype, which has been shown to have the worst oncologic outcomes but most sensitivity to ADT. [ABSTRACT FROM AUTHOR]