title: Immunohistochemical distinction of invasive from noninvasive breast lesions: a comparative study of p63 versus calponin and smooth muscle myosin heavy chain.
abstract: Identification of myoepithelial cells using antibodies to cytoskeletal proteins, such as smooth muscle myosin heavy chain (SMM-HC) and calponin, can play an important role in distinguishing invasive carcinoma from its histologic mimics. However, antibodies to these proteins may also cross-react with stromal myofibroblasts and vascular smooth muscle cells. It has recently been demonstrated that myoepithelial cells express the nuclear protein, p63, a member of the p53 gene family. We compared the patterns of reactivity of antibodies with p63, calponin, and SMM-HC on 85 breast lesions, including 11 cases of sclerosing adenosis, 33 cases of ductal carcinoma in situ, including 10 that showed microinvasion, 6 cases of lobular carcinoma in situ, and 35 cases of infiltrating ductal carcinoma. All three antibodies were positive on the vast majority of myoepithelial cells in all cases. A small minority of cases showed focal gaps in the revealed myoepithelial cell layer, reflected in discontinuous positive immunostaining around noninvasive epithelial nests (including ductal carcinoma in situ). No case showed p63 expression by myofibroblasts or vascular smooth muscle cells, whereas myofibroblasts expressed, in 8% and 76% of cases, SMM-HC and calponin, respectively. Although no tumor cell reactivity was noted with antibodies to calponin or SMM-HC, tumor cells in 11% of cases showed at least focal p63 expression. And although antibodies to p63 offer excellent sensitivity and increased specificity for myoepithelial detection relative to antibodies to calponin and SMM-HC, they have the following diagnostic limitations: 1) they occasionally demonstrate an apparently discontinuous myoepithelial layer, particularly around ductal carcinoma in situ, and 2) they react with a small but significant subset of breast carcinoma tumor cells. p63 may represent a myoepithelial marker that can complement or replace SMM-HC and/or calponin in the analysis of difficult breast lesions.
authors.affiliation: PhenoPath Laboratories, Seattle, Washington, 98103, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Werling
authors.forename: Harry
authors.initials: H
authors.lastname: Hwang
authors.forename: Hadi
authors.initials: H
authors.lastname: Yaziji
authors.forename: Allen M
authors.initials: AM
authors.lastname: Gown
mesh_terms: D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000737:chemistry* / Q000473:pathology; D002135:Calcium-Binding Proteins / Q000032:analysis*; D002277:Carcinoma / Q000737:chemistry* / Q000473:pathology; D002278:Carcinoma in Situ / Q000737:chemistry / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000737:chemistry / Q000473:pathology; D002285:Carcinoma, Intraductal, Noninfiltrating / Q000737:chemistry / Q000473:pathology; D018275:Carcinoma, Lobular / Q000737:chemistry / Q000473:pathology; D004268:DNA-Binding Proteins; D003937:Diagnosis, Differential; D005260:Female; D005348:Fibrocystic Breast Disease / Q000737:chemistry / Q000473:pathology; D016147:Genes, Tumor Suppressor; D006801:Humans; D007124:Immunoenzyme Techniques / Q000379:methods; D008565:Membrane Proteins; D008840:Microfilament Proteins; D009130:Muscle, Smooth / Q000737:chemistry; D018995:Myosin Heavy Chains / Q000032:analysis*; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000032:analysis; D010750:Phosphoproteins / Q000032:analysis*; D012680:Sensitivity and Specificity; D024745:Smooth Muscle Myosins / Q000032:analysis; D015534:Trans-Activators / Q000032:analysis*; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000096985:Calponins
chemical_list: D014408:Biomarkers, Tumor; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins; D018995:Myosin Heavy Chains; D009363:Neoplasm Proteins; D010750:Phosphoproteins; D024745:Smooth Muscle Myosins; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D000096985:Calponins; C081876:CKAP4 protein, human; C115051:TP63 protein, human