Abstract

An adequate reproducibility in the description of tissue architecture is still a challenge to diagnostic pathology, sometimes with unfortunate prognostic implications. To assess a possible diagnostic and prognostic value of quantitiative tissue architecture analysis, structural features based on the Voronoi Diagram (VD) and its subgraphs were developed and tested.A series of 27 structural features were developed and tested in a pilot study of 30 cases of prostate cancer, 10 cases of cervical carcinomas, 8 cases of tongue cancer and 8 cases of normal oral mucosa. Grey level images were acquired from hematoxyline‐eosine (HE) stained sections by a charge coupled device (CCD) camera mounted on a microscope connected to a personal computer (PC) with an image array processor. From the grey level images obtained, cell nuclei were automatically segmented and the geometrical centres of cell nuclei were computed. The resulting 2‐dimensional (2D) swarm of pointlike seeds distributed in a flat plane was the basis for construction of the VD and its subgraphs. From the polygons, triangulations and arborizations thus obtained, 27 structural features were computed as numerical values. Comparison of groups (normal vs. cancerous oral mucosa, cervical and prostate carcinomas with good and poor prognosis) with regard to distribution in the values of the structural features was performed with Student's t‐test.We demonstrate that some of the structural features developed are able to distinguish structurally between normal and cancerous oral mucosa (P=0.001), and between good and poor outcome groups in prostatic (P=0.001) and cervical carcinomas (P=0.001).We present results confirming previous findings that graph theory based algorithms are useful tools for describing tis‐ sue architecture (e.g., normal versus malignant). The present study also indicates that these methods have a potential for prognostication in malignant epithelial lesions.

Highlights

  • Several authors have demonstrated that subjective grading of malignant lesions is associated with poor reproducibility and with reduced prognostic power [1,2,3,4,5], some indicate the opposite [6]

  • Eight biopsies from assumptively normal oral mucosa and 8 cases of oral carcinomas of the tongue were compared with regard to values of 10 structural features

  • 6 features made it possible to distinguish between normal oral mucosa and carcinoma of the tongue, usually situated at the lateral border of tongue, bordering onto the floor of the mouth

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Summary

Introduction

Several authors have demonstrated that subjective grading of malignant lesions is associated with poor reproducibility and with reduced prognostic power [1,2,3,4,5], some indicate the opposite [6]. We have undertaken the present study in order to develop tools for fast, strictly quantitiative and reproducible tissue architecture analysis in epithelial tissues (squamous cell carcinomas from the prostate, cervix and oral cavity and normal oral mucosa) and to evaluate the diagnostic and prognostic potential of these methods in such tissues By employing graphs such as the Voronoi Diagram (VD [Figs 1–4]) [33] and its subgraphs, the Delaunay Triangulation (DT [Fig. 2]), Minimum Spanning Tree (MST [Fig. 5]) [34,35,36,37,38], Ulam Tree (UT [Fig. 6]) [39] and the Gabriel Graph (GG [Fig. 7]) [40], the structural manifestations of cellular interactions in tissues may be quantified [41,42,43,44,45,46,47]. A total of 27 structural features were developed, taking into consideration the shape of individual structural entities (polygons, triangulations, arborizations), derived from the VD; clusterings, from the GG, and studying the order or randomness in the distribution of pointlike seeds, derived from the UT and MST

Material
Data acquisition
Segmentation
Building a composite picture
Space partitioning
Topographical analysis
Border effects
Temporal aspects
Results
Discussion
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