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

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 (n = 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 500 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.

Three‐dimensional architecture of common benign and precancerous prostate epithelial lesions

“…Benign and malignant prostate lesions can show overlapping morphological features on H&E slides. However, we found that the 3D architecture of most benign epithelial lesions was entirely different . For instance, simple and partial atrophy might closely resemble PCa on H&E and immunohistochemical stained slides, showing partial loss of basal cells .…”

“…These formed a disorganised network composed of luminal cells only and had no basal cell layer (Figure C,D). For a complete and comprehensive description of the 3D architecture of prostate adenocarcinoma growth patterns, we refer to our previous study …”

“…However, we found that the 3D architecture of most benign epithelial lesions was entirely different. 10,14 For instance, simple and partial atrophy might closely resemble PCa on H&E and immunohistochemical stained slides, showing partial loss of basal cells. 8 However, their 3D structure showed that these lesions clearly retain an acinar organisation, which is disrupted in PCa.…”

“…For a complete and comprehensive description of the 3D architecture of prostate adenocarcinoma growth patterns, we refer to our previous study. 14…”

Advances in Ex Situ Tissue Optical Clearing

“…Recently, the same group has extended this solvent‐based approach. Using iDISCO protocols they characterized 3D architecture of both benign and pre‐cancerous prostate lesions and described two distinct growth patterns of prostate cancer in patients . Notably, no group has taken up the matter of TOC of penis which, assumingly, would be valuable for deciphering of blood vessels and innervations patterns, with possible application to improve understanding of, for example, severe cases of erectile dysfunction.…”