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Three-dimensional analysis reveals two major architectural subgroups of prostate cancer growth patterns.

Authors :
Verhoef EI
van Cappellen WA
Slotman JA
Kremers GJ
Ewing-Graham PC
Houtsmuller AB
van Royen ME
van Leenders GJLH
Source :
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2019 Jul; Vol. 32 (7), pp. 1032-1041. Date of Electronic Publication: 2019 Feb 08.
Publication Year :
2019

Abstract

The Gleason score is one of the most important parameters for therapeutic decision-making in prostate cancer patients. Gleason growth patterns are defined by their histological features on 4- to 5-µm cross sections, and little is known about their three-dimensional architecture. Our objective was to characterize the three-dimensional architecture of prostate cancer growth patterns. Intact tissue punches (nā€‰=ā€‰46) of representative Gleason growth patterns from radical prostatectomy specimens were fluorescently stained with antibodies targeting Keratin 8/18 and Keratin 5 for the detection of luminal and basal epithelial cells, respectively. Punches were optically cleared in benzyl alcohol-benzyl benzoate and imaged using a confocal laser scanning microscope up to a depth of 500ā€‰µm. Gleason pattern 3, poorly formed pattern 4, and cords pattern 5 all formed a continuum of interconnecting tubules in which the diameter of the structures and the lumen size decreased with higher grades. In fused pattern 4, the interconnections between the tubules were markedly closer together. In these patterns, all tumor cells were in direct contact with the surrounding stroma. In contrast, cribriform Gleason pattern 4 and solid pattern 5 demonstrated a three-dimensional continuum of contiguous tumor cells, in which the vast majority of cells had no contact with the surrounding stroma. Transitions between cribriform pattern 4 and solid pattern 5 were seen. There was a decrease in the number and size of intercellular lumens from cribriform to solid growth pattern. Glomeruloid pattern 4 formed an intermediate structure consisting of a tubular network with intraluminal epithelial protrusions close to the tubule splitting points. In conclusion, three-dimensional microscopy revealed two major architectural subgroups of prostate cancer growth patterns: (1) a tubular interconnecting network including Gleason pattern 3, poorly formed and fused Gleason pattern 4, and cords Gleason pattern 5, and (2) serpentine contiguous epithelial proliferations including cribriform Gleason pattern 4 and solid Gleason pattern 5.

Details

Language :
English
ISSN :
1530-0285
Volume :
32
Issue :
7
Database :
MEDLINE
Journal :
Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc
Publication Type :
Academic Journal
Accession number :
30737469
Full Text :
https://doi.org/10.1038/s41379-019-0221-0