3D-reconstruction of prostate cancer architecture with serial immunohistochemical sections: hallmarks of tumour growth, tumour compartmentalization and implications for grading and heterogeneity

Abstract

Background

Conventional morphology of the prostate cancer (PCA) considers only two-dimensional architecture of the tumour. Our aim was to examine the feasibility of 3D-reconstruction of tumour morphology based on multiple consecutive histological sections and to decipher relevant features of PCA architecture.

Methods

Seventy-five consecutive histological sections (5μm) of a typical prostate adenocarcinoma (Gleason-Score 3+4=7) were immunostained (Pan-Cytokeratin) and scanned for further 3D reconstructions with Fiji / ImageJ software.

Results

The main findings related to the PCA architecture in this case are: 1) Continuity of all glands with tumour being an integrative system, even in Gleason pattern 4 (GP4) with poor formed glands; no short range migration of cells by GP4 (poor formed glands); 2) No repeated interconnections between the glands with a tumour building a tree-like branched structure with very "plastic" branches (maximal depth of investigation 375 μm); 3) very stark compartmentalization of the tumour related to extensive branching, co-existence of independent terminal units of such branches in one 2D-slice explaining intratumoural heterogeneity. 4) Evidence of cranio-caudal growth vector in interglandular regions of the prostate and for latero-medial growth vector in subcapsular posterolateral regions, 5) 3D architecture-based description of the GP4 with poor formed glands, its continuum with GP3.

Conclusions

Consecutive histological sections provide a high-quality material for 3D reconstructions of the tumour architecture with excellent resolution. The reconstruction of multiple regions in this typical case of a Gleason score 3+4=7 tumour provided insights in relevant aspects of tumour growth, continuity of Gleason patterns 3 and 4 and tumour heterogeneity.

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