title: Morphological and immunophenotypic analysis of breast carcinomas with basal and myoepithelial differentiation.
abstract: The aim of this study was to assess the morphological characteristics and immunohistochemical profile of breast carcinomas with basal and myoepithelial phenotypes to obtain a better understanding of their biological behaviour and nature. One thousand nine hundred and forty-four invasive breast carcinomas were examined, using tissue microarray (TMA) technology and immunohistochemistry, to identify those tumours that showed basal and myoepithelial phenotypes, and their immunophenotype profile was characterized using a variety of markers. In addition, haematoxylin and eosin-stained sections of these tumours were studied for several morphological parameters. The findings were correlated with patient and tumour characteristics and outcome data. Tumours were classified into two groups: (1) tumours with basal phenotype [expressing one or both basal markers (CK5/6 and/or CK14)] and (2) tumours with myoepithelial phenotype (expressing SMA and/or p63). Group 1 was further subdivided into two subgroups: (A) dominant basal pattern (more than 50% of cells positive) and (B) basal characteristics (10-50% of cells positive). Group 1 tumours constituted 18.6% (8.6% and 10% for groups 1A and 1B, respectively) and group 2 constituted 13.7% of the cases. In both groups, the most common histological types were ductal/no specific type, tubular mixed and medullary-like carcinomas; the majority of these tumours were grade 3. There were positive associations with adenoid cystic growth pattern, loss of tubule formation, marked cellular pleomorphism, poorer Nottingham prognostic index, and development of distant metastasis. In addition, associations were found with loss of expression of steroid hormone receptors and FHIT proteins and positive expression of p53 and EGFR. The most common characteristics in group 1 were larger size, high-grade comedo-type necrosis, development of tumour recurrence, and absence of lymph node disease. Group 2 tumours were more common in younger patients and were associated with central acellular zones, basaloid change, and positive E-cadherin protein expression. Group 1 characteristics were associated with both reduced overall survival (OS) [log rank (LR) = 22.5, p < 0.001] and reduced disease-free interval (DFI) (LR = 30.1, p < 0.001), while group 2 characteristics showed an association with OS (LR = 5, p = 0.02) but not with DFI. Multivariate analysis showed that basal, but not myoepithelial, phenotype has an independent value in predicting outcome. Breast cancers with basal and myoepithelial phenotypes are distinct groups of tumours that share some common morphological features and an association with poor prognosis. The basal rather than the myoepithelial phenotype has the strongest relationship with patient outcome.
authors.affiliation: Department of Histopathology, Nottingham City Hospital NHS Trust and University of Nottingham, UK.
authors.forename: E A
authors.initials: EA
authors.lastname: Rakha
authors.forename: T C
authors.initials: TC
authors.lastname: Putti
authors.forename: D M
authors.initials: DM
authors.lastname: Abd El-Rehim
authors.forename: C
authors.initials: C
authors.lastname: Paish
authors.forename: A R
authors.initials: AR
authors.lastname: Green
authors.forename: D G
authors.initials: DG
authors.lastname: Powe
authors.forename: A H
authors.initials: AH
authors.lastname: Lee
authors.forename: J F
authors.initials: JF
authors.lastname: Robertson
authors.forename: I O
authors.initials: IO
authors.lastname: Ellis
mesh_terms: D000199:Actins / Q000235:genetics; D000328:Adult; D000367:Age Factors; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis; D001943:Breast Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D015820:Cadherins / Q000032:analysis; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D002454:Cell Differentiation; D018572:Disease-Free Survival; D066246:ErbB Receptors / Q000032:analysis; D005260:Female; D016158:Genes, p53; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000235:genetics; D008875:Middle Aged; D015999:Multivariate Analysis; D009208:Myoepithelioma / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D009336:Necrosis; D018295:Neoplasms, Basal Cell / Q000276:immunology / Q000401:mortality / Q000473:pathology*; D011944:Receptors, Androgen / Q000032:analysis; D013194:Staining and Labeling; D015996:Survival Rate
chemical_list: D000199:Actins; D014408:Biomarkers, Tumor; D015820:Cadherins; D011944:Receptors, Androgen; D007633:Keratins; D066246:ErbB Receptors