Abstract
Intraductal carcinoma of the prostate (IDC-P) is a rare and unique form of aggressive prostate carcinoma, which is characterized by an expansile proliferation of malignant prostatic epithelial cells within prostatic ducts or acini and the preservation of basal cell layers around the involved glands. The vast majority of IDC-P tumors result from adjacent high-grade invasive cancer via the retrograde spreading of tumor cells into normal prostatic ducts or acini. A subset of IDC-P tumors is rarely derived from the de novo intraductal proliferation of premalignant cells. The presence of IDC-P in biopsy or surgical specimens is significantly associated with aggressive pathologic features, such as high Gleason grade, large tumor volume, and advanced tumor stage, and with poor clinical courses, including earlier biochemical recurrence, distant metastasis, and worse survival outcomes. These architectural and behavioral features of IDC-P may be driven by specific molecular properties. Notably, IDC-P possesses distinct genomic profiles, including higher rates of TMPRSS2–ERG gene fusions and PTEN loss, increased percentage of genomic instability, and higher prevalence of germline BRCA2 mutations. Considering that IDC-P tumors are usually resistant to conventional therapies for prostate cancer, further studies should be performed to develop optimal therapeutic strategies based on distinct genomic features, such as treatment with immune checkpoint blockades or poly (adenosine diphosphate–ribose) polymerase inhibitors for patients harboring increased genomic instability or BRCA2 mutations, as well as genetic counseling with genetic testing. Patient-derived xenografts and tumor organoid models can be the promising in vitro platforms for investigating the molecular features of IDC-P tumor.
Highlights
LobaccaroDepartment of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul 06351, Korea Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University These authors contributed equally to this work
intraductal carcinoma of the prostate (IDC-P) shares immunohistochemical features, such as positive staining of prostatespecific antigen and alpha-methylacyl-CoA racemase, with high-grade prostatic intraepithelial neoplasia (HGPIN), which is known as precancerous lesion of prostate cancer (PCa) [30]
Patients with precursor-like IDC-P had better clinicopathological features and longer biochemical recurrence (BCR)-free survival than those with classical IDC-P [38]. Consistent with these findings, Khani et al [24] demonstrated that IDC-P without invasive tumors had good clinical prognosis and distinct molecular features, such as a striking number (57%) of enrichments in oncogenic driver mutations in MAPK/PI3K pathway genes in targeted sequencing, which are rare in conventional prostate adenocarcinoma
Summary
Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, Seoul 06351, Korea Department of Digital Health, SAIHST, Sungkyunkwan University, Seoul 06351, Korea Department of Pathology and Translational Genomics, Samsung Medical Center, Sungkyunkwan University These authors contributed equally to this work.
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