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01-12-2020 | Breast Cancer | Research article

Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients

Authors: Laurent Gole, Joe Yeong, Jeffrey Chun Tatt Lim, Kok Haur Ong, Hao Han, Aye Aye Thike, Yong Cheng Poh, Sidney Yee, Jabed Iqbal, Wanjin Hong, Bernett Lee, Weimiao Yu, Puay Hoon Tan

Published in: Breast Cancer Research | Issue 1/2020

Abstract

Background

Stromal and collagen biology has a significant impact on tumorigenesis and metastasis. Collagen is a major structural extracellular matrix component in breast cancer, but its role in cancer progression is the subject of historical debate. Collagen may represent a protective layer that prevents cancer cell migration, while increased stromal collagen has been demonstrated to facilitate breast cancer metastasis.

Methods

Stromal remodeling is characterized by collagen fiber restructuring and realignment in stromal and tumoral areas. The patients in our study were diagnosed with triple-negative breast cancer in Singapore General Hospital from 2003 to 2015. We designed novel image processing and quantification pipelines to profile collagen structures using numerical imaging parameters. Our solution differentiated the collagen into two distinct modes: aggregated thick collagen (ATC) and dispersed thin collagen (DTC).

Results

Extracted parameters were significantly associated with bigger tumor size and DCIS association. Of numerical parameters, ATC collagen fiber density (CFD) and DTC collagen fiber length (CFL) were of significant prognostic value for disease-free survival and overall survival for the TNBC patient cohort. Using these two parameters, we built a predictive model to stratify the patients into four groups.

Conclusions

Our study provides a novel insight for the quantitation of collagen in the tumor microenvironment and will help predict clinical outcomes for TNBC patients. The identified collagen parameters, ATC CFD and DTC CFL, represent a new direction for clinical prognosis and precision medicine. We also compared our result with benign samples and DICS samples to get novel insight about the TNBC heterogeneity. The improved understanding of collagen compartment of TNBC may provide insights into novel targets for better patient stratification and treatment.

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Title: Quantitative stain-free imaging and digital profiling of collagen structure reveal diverse survival of triple negative breast cancer patients
Authors: Laurent Gole
Joe Yeong
Jeffrey Chun Tatt Lim
Kok Haur Ong
Hao Han
Aye Aye Thike
Yong Cheng Poh
Sidney Yee
Jabed Iqbal
Wanjin Hong
Bernett Lee
Weimiao Yu
Puay Hoon Tan
Publication date: 01-12-2020
Publisher: BioMed Central
Keywords: Breast Cancer
Breast Cancer
Published in: Breast Cancer Research / Issue 1/2020
Electronic ISSN: 1465-542X
DOI: https://doi.org/10.1186/s13058-020-01282-x

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Abstract

Background

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Conclusions

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