Introduction: Prostate cancer (PCa) is the most diagnosed cancer in North American men varying greatly at clinical presentation from indolent to aggressive tumors. An aggressive subtype of PCa is intraductal carcinoma of the prostate (IDC-P), identified in ~20% of men with PCa. While accurate stratification of these high-risk patients is a clinical necessity, the question arose whether IDC-P could be related to the grade or not. We hypothesized that through the genomic characterization of IDC-P, we could explore the link between IDC-P, grade, and or stage. The objective of this study was to characterize the copy number alterations (CNAs) of IDC-P to aid in the characterization of these high-risk men, while exploring whether IDC-P should be integrated into the grade or stage of PCa. Methods: We selected 462 radical prostatectomy specimens obtained through The Cancer Genome Atlas (TCGA). Specifically, 38 patients were excluded from the original TCGA cohort (n=500) due to stage T4 and incomplete genomic data. We further characterized the TCGA cohort by identifying the IDC-P status (present or not identified) for each patient through the online available tissue. For each patient, IDC-P status was evaluated alongside the CNAs of 488 genes involved in androgen receptor signaling and or carcinogenesis. Results: Out of 462 patients, 41% (191/462) were IDC-P present, and these patients were mostly of high grade (53.9%) and advanced pT3b stage (38.7%). Overall, 38 genes were significantly associated to IDC-P growth, of which, 37 genes were novel and not unique to IDC-P or documented in PCa. Specifically, 10 genes were associated to chromosome 10q deletions, including the well-recognized PTEN, while 28 genes were associated to chromosome 8q amplifications. Of the IDC-P present men identified, 36% (69/191) of these men had multiple deletions and 16% (31/191) of these men had multiple amplifications. Conclusions: We found significant deletions in 10 genes and amplifications in 28 genes in IDC-P. Importantly, high-risk men with IDC-P have numerous deletions and amplifications in the identified 38 genes. We have identified novel genes, except for PTEN. Indeed, more than 2/3 of these genes are amplified on 8q and their expression could be targeted as biomarkers of IDC-P. We are exploring the presence of these anomalies in PCa and their relation to Grade group (especially cribriform pattern) and or stage. Together, these findings will genomically characterize IDC-P and allow for improved precision in the stratification of these high-risk patients. SOURCE OF Funding: Institut du Cancer de Montréal.
.jpg "Helen Pantazopoulos, BS,MSC photo")