Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy.

Andrea J Clark,Howard R Petty

doi:10.1038/srep27039

Abstract

Although epidemiological studies propose aggressive and non-aggressive forms of ductal carcinoma in situ (DCIS), they cannot be identified with conventional histopathology. We now report a retrospective study of human biopsy samples using biomarker ratio imaging microscopy (BRIM). Using BRIM, micrographs of biomarkers whose expression correlates with breast cancer aggressiveness are divided by micrographs of biomarkers whose expression negatively correlates with aggressiveness to create computed micrographs reflecting aggressiveness. The biomarker pairs CD44/CD24, N-cadherin/E-cadherin, and CD74/CD59 stratified DCIS samples. BRIM identified subpopulations of DCIS lesions with ratiometric properties resembling either benign fibroadenoma or invasive carcinoma samples. Our work confirms the existence of distinct subpopulations of DCIS lesions, which will likely have utility in breast cancer research and clinical practice.

Highlights

Our studies demonstrate that biomarker ratio imaging microscopy (BRIM) stratifies Ductal carcinoma in situ (DCIS) samples
Screening tools for cervical and colorectal cancer reduced the incidence of advanced forms of these diseases, screening mammography has not yielded a similar reduction in advanced breast cancer[1,2,3]
Our BRIM studies using biomarkers of breast cancer aggressiveness have identified DCIS subtypes thereby confirming the postulate of Esserman and others regarding the heterogeneity of DCIS subtypes

Summary

Introduction

CD44hi/CD24lo cells could not be observed in a sub-population DCIS samples (see below). On the basis of prior biomarker research[19,20,21], we studied CD74hi/CD59lo cells in DCIS samples. We first compared pixel intensity histograms of control breast tissue (white region; low BRIM value) with DCIS tissue expressing aggressive biomarker properties (black region; high BRIM value); gray values >130 were only found in the DCIS sample (Fig. 2F).

Results

Conclusion