Digital differentiation of non-small cell carcinomas of the lung by the fractal dimension of their epithelial architecture

Lik Hang Lee; Mauro Tambasco; Shannon Otsuka; Allison Wright; Alexander Klimowicz; Stephanie Petrillo; Don Morris; Anthony Magliocco; D Gwyn Bebb

doi:10.1016/j.micron.2014.07.005

Digital differentiation of non-small cell carcinomas of the lung by the fractal dimension of their epithelial architecture

Micron. 2014 Dec:67:125-131. doi: 10.1016/j.micron.2014.07.005. Epub 2014 Jul 28.

Authors

Lik Hang Lee¹, Mauro Tambasco², Shannon Otsuka³, Allison Wright³, Alexander Klimowicz⁴, Stephanie Petrillo⁴, Don Morris³, Anthony Magliocco⁵, D Gwyn Bebb⁶

Affiliations

¹ Department of Pathology and Laboratory Medicine, University of Calgary, 1403 29 Street NW, Calgary, AB, Canada T2N 2T9.
² Department of Physics and Astronomy, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4; Department of Oncology, University of Calgary and Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, AB, Canada T2 N 4N2.
³ Department of Oncology, University of Calgary and Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, AB, Canada T2 N 4N2.
⁴ Functional Tissue Imaging Unit, Translational Research Laboratory, Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, AB, Canada T2 N 4N2.
⁵ Department of Pathology and Laboratory Medicine, University of Calgary, 1403 29 Street NW, Calgary, AB, Canada T2N 2T9; Department of Physics and Astronomy, University of Calgary, 2500 University Drive NW, Calgary, AB, Canada T2N 1N4.
⁶ Department of Oncology, University of Calgary and Tom Baker Cancer Centre, 1331 29 Street NW, Calgary, AB, Canada T2 N 4N2. Electronic address: Gwyn.Bebb@albertahealthservices.ca.

PMID: 25151215
DOI: 10.1016/j.micron.2014.07.005

Abstract

Introduction: In recent years, differences have emerged in the treatment of squamous and non-squamous non-small cell lung carcinomas (NSCLCs). This highlights the importance of accurate histopathologic classification. However, there remains inter-observer disagreement when making diagnoses based on histology. Fractal dimension (FD) is a mathematical measure of irregularity and complexity of shape. We hypothesize that the FD of carcinoma epithelial architecture can assist in differentiating adenocarcinoma (ADC) from squamous cell carcinoma (SCC) of the lung.

Methods: 134 resected (88 ADC and 46 SCC) cases of resected early-stage NSCLC were analyzed. Tissue micro arrays were generated from formalin-fixed paraffin-embedded tissue, stained with pan-cytokeratin, and digitally imaged and the FD of the epithelial structure calculated. Mean FD of ADC and SCC were compared using the independent t-test, partial correlations, and receiver operating characteristic (ROC) analyses.

Results: A statistically significant difference (p<0.001) between the mean FD of ADC (M=1.70, SD=0.07) and SCC (M=1.78, SD=0.07) was found. Significance remained (p<0.001) when controlling for several possible confounders. ROC analysis demonstrated an area-under-the-curve of 0.81 (p<0.001).

Conclusions: The epithelial structure FD of NSCLC has potential as a reproducible and automated measure to help subtype NSCLCs into ADC and SCC. With further image analysis algorithm improvements, fractal analysis may be a component in computerized histomorphological assessments of lung cancer and may provide an adjunct test in differentiating NSCLCs.

Keywords: Carcinoma; Digital imaging; Digital microscopy; Fractal analysis; Histology; Lung.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adenocarcinoma / ultrastructure
Aged
Carcinoma, Non-Small-Cell Lung / diagnosis
Carcinoma, Non-Small-Cell Lung / ultrastructure*
Female
Fractals
Humans
Image Processing, Computer-Assisted
Kaplan-Meier Estimate
Lung Neoplasms / diagnosis
Lung Neoplasms / ultrastructure*
Male
Middle Aged
Respiratory Mucosa / ultrastructure*
Sensitivity and Specificity