Spatial Characteristics of Intraductal Carcinoma of the Prostate

Intraductal carcinoma of the prostate (IDC-P) is most often considered a retrograde spread of invasive prostate cancer (PCa) into prostatic ducts, and its presence is associated with a poor prognosis. The aim of our study was to evaluate the differential expression between IDC-P and the associated invasive component and the heterogeneity of expression within IDC-P foci.

We studied 79 cases of PCa with an intraductal component treated by prostatectomy. TMA blocks were constructed with the intraductal and invasive components and used for immunohistochemical analysis of markers involved in the cell cycle, androgen signaling, hypoxia, DNA repair, and immune checkpoints.

We found a good concordance of expression between both components for ERG, PTEN, p53, and MMR genes, which nevertheless show in some cases a loss restricted to the intraductal component. The expression of Ki67, PD-L1, and GLUT1 was increased in IDP-C compared to the invasive component. Furthermore, spatial heterogeneity was observed in the intraductal component: Ki67, ERG, androgen receptor and p53 were more expressed in the periphery of the lesion, while the expression of PD-L1 and GLUT1 was restricted to the center.

Our results support a relatedness between invasive PCa and IDC-P, and show increased expression of markers related to PCa aggressiveness in the intraductal component. The spatial heterogeneity within IDC-P suggests a higher degree of hypoxia in the center of the lesion. Increased PD-L1 expression and loss of expression of some MMR genes in IDC-P could lead to increased sensitivity to immunomodulatory treatments.