title: Identification of lesion subtypes in biopsies of ductal carcinoma in situ of the breast using biomarker ratio imaging microscopy.
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.
authors.affiliation: Department of Ophthalmology and Visual Sciences, 1000 Wall Street, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Andrea J
authors.initials: AJ
authors.lastname: Clark
authors.affiliation: Department of Ophthalmology and Visual Sciences, 1000 Wall Street, University of Michigan Medical School, Ann Arbor, MI, USA.
authors.forename: Howard R
authors.initials: HR
authors.lastname: Petty
mesh_terms: D000906:Antibodies / Q000737:chemistry; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D000944:Antigens, Differentiation, B-Lymphocyte / Q000235:genetics / Q000378:metabolism; D014408:Biomarkers, Tumor / Q000235:genetics* / Q000378:metabolism; D001706:Biopsy; D001943:Breast Neoplasms / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D051927:CD24 Antigen / Q000235:genetics / Q000378:metabolism; D018957:CD59 Antigens / Q000235:genetics / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D003937:Diagnosis, Differential; D005260:Female; D018226:Fibroadenoma / Q000145:classification / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D015870:Gene Expression; D000949:Histocompatibility Antigens Class II / Q000235:genetics / Q000378:metabolism; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D008853:Microscopy / Q000379:methods*; D008875:Middle Aged; D012189:Retrospective Studies
chemical_list: D000906:Antibodies; D015703:Antigens, CD; D000944:Antigens, Differentiation, B-Lymphocyte; D014408:Biomarkers, Tumor; D051927:CD24 Antigen; C497889:CD24 protein, human; C497483:CD44 protein, human; D018957:CD59 Antigens; C513384:CDH1 protein, human; C050361:CDH2 protein, human; D015820:Cadherins; D000949:Histocompatibility Antigens Class II; D018960:Hyaluronan Receptors; C045084:invariant chain; C051590:CD59 protein, human