Improved differentiation between ductal and acinar prostate cancer using three-dimensional histology and biomarkers.

Objective: The aim of the study was to refine the methodology for discriminating the ductal (DAP) and acinar adenocarcinomas (AAP) of the prostate and confirm that prostate carcinoma of ductal origin is a more aggressive subtype.

Material and methods: A retrospective analysis of 110 consecutive radical prostatectomy cases operated on between 2000 and 2006 and worked up using large-format "two-dimensional" (2D; 4 μm thick) and "three-dimensional" (3D; 1500 μm thick) histology sections was carried out, with an average follow-up of 5.1 years. The same material was also analysed for selected biomarkers in tissue microarray blocks. The most discriminatory biomarkers were then tested on preoperative core biopsy specimens from 24 of these patients.

Results: 3D histology classified 97/110 (88%) cases of AAP and 13/110 (12%) DAP, which was then confirmed in 2D specimens. The DAP cases had a significantly greater frequency of pT3a and more advanced cancers, > 20 mm tumour focus, high-grade prostatic intraepithelial neoplasia, Gleason score ≥ 7, positive margin, extracapsular extension, vascular invasion, seminal vesicle infiltration, biochemical/local recurrence, regional lymph-node metastases and distant metastases. Three biomarkers in combination (chromogranin A, epidermal growth factor receptor and p53] distinguished DAP from AAP with an accuracy of 94% (area under the curve 0.94, 95% confidence interval 0.88-0.99). The same high accuracy was achieved using these three biomarkers on the preoperative specimens.

Conclusions: Both 3D histology and the three selected biomarkers can help in accurately distinguishing DAP from AAP. The clear-cut distinction of two forms of prostate cancers by the approach advocated in this paper would allow AAP patients to undergo less radical treatment and would segregate DAP patients into a subset requiring more effective treatment regimens.