Genomic Features and Clinical Implications of Intraductal Carcinoma of the Prostate

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.

Keywords: clinical implication; genomic feature; intraductal carcinoma; prostate cancer.

Figure 1

Representative images of hematoxylin and eosin staining for (A) classic and (B) isolated forms of intraductal carcinoma of the prostate (IDC-P) from the cases of the authors′ institution. (A) Cribriform tumor spreads into a non-neoplastic gland lined by a layer of basal cells in a 50 year old patient with pT3b prostate cancer. Initial PSA was 29.22 ng/mL. The Gleason score of invasive adenocarcinoma was 4 + 3 = 7/10. (B) Intraductal proliferation shows epithelial atypia surpassing that of high-grade prostatic intraepithelial neoplasia (HGPIN) not accompanied by invasive adenocarcinoma elsewhere in an 80 year old patient. Initial PSA was 7.09 ng/mL.