Molecular Alterations in Intraductal Carcinoma of the Prostate

Simple Summary Intraductal carcinoma of the prostate (IDC-P) is a neoplastic proliferation within the prostatic ducts with a retained basal cell layer that exceeds the usual extent of precursor lesions. IDC-P may be present either in association with high-grade prostate cancer or independently of any high-grade cancer or invasive tumor. In this review, we focus on molecular alterations that are present in IDC-P with or without concomitant high-grade cancer as well as genetic alterations present in men that may lead to the development of IDC-P.Abstract Intraductal carcinoma of the prostate is most commonly associated with high-grade invasive prostate cancer. However, isolated IDC-P without adjacent cancer or high-grade cancer is also well known. Common genetic alterations present in IDC-P with adjacent high-grade prostate cancer are those described in high-grade tumors, such as PTEN loss (69-84%). In addition, the rate of LOH involving TP53 and RB1 is significantly higher. IDC-P is common in the TCGA molecular subset of SPOP mutant cancers, and the presence of SPOP mutations are more likely in IDC-P bearing tumors. IDC-P without adjacent high-grade cancers are by far less common. They are less likely to have PTEN loss (47%) and rarely harbor an ERG fusion (7%). Molecular alterations that may predispose a person to the development of IDC-P include the loss of BRCA2 and PTEN as well as mutations in SPOP. However, the causative nature of these genetic alterations is yet to be validated.