Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors
Autor: | Åke Borg, Niklas Loman, Mervi Laakso, Jorma Isola |
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Rok vydání: | 2005 |
Předmět: |
Pathology
medicine.medical_specialty Receptor ErbB-2 Population Breast Neoplasms Biology Pathology and Forensic Medicine Cohort Studies Basal (phylogenetics) Cytokeratin Breast cancer Immunophenotyping Carcinoma medicine Humans Genes Tumor Suppressor Neoplasm Invasiveness education education.field_of_study BRCA1 Protein Tumor Suppressor Proteins Carcinoma Ductal Breast Myoepithelial cell Genes erbB-2 Middle Aged Phosphoproteins medicine.disease Immunohistochemistry DNA-Binding Proteins Phenotype Trans-Activators Keratins Female Transcription Factors |
Zdroj: | Modern Pathology. 18:1321-1328 |
ISSN: | 0893-3952 |
DOI: | 10.1038/modpathol.3800456 |
Popis: | Breast ducts contain two types of epithelial cells, inner luminal cells and outer basal/myoepithelial cells. These cells can be distinguished by their immunophenotype. Cytokeratins (CKs) 8 and 18 are expressed in the luminal layer, whereas CK5/14 and the transcription factor p63 characterize the basal epithelial layer. We studied a population-based cohort of 288 sporadic ductal invasive cancers and found 9% positive for CK5/14 and 4% positive for p63. Using a highly sensitive polymer-based immunohistochemical staining, all sporadic tumors were positive for the luminal CK8/18, including those positive for CK5/14. Pairs of primary tumors and metastases (n = 38) were always concordant for CK5/14 expression. The majority of the CK5/14-positive cases were of histologic grade III (P = 0.0007) and steroid hormone receptor negative (P < 0.0001). CK5/14 expression was inversely associated with HER-2 oncogene amplification, but only in the subgroup of estrogen receptor-negative tumors (P = 0.007). In a separate set of 42 hereditary breast cancers, the majority (78%) of the BRCA1-associated tumors, but only one of 15 BRCA2-associated tumors was positive for CK5/14. In contrast to sporadic CK5/14-positive tumors, BRCA1-associated tumors displayed less intense CK8/18 staining, including some truly CK5/14-positive CK8/18-negative cases. These results suggest that CK5/14-positive sporadic breast cancers arise from glandularly committed progenitor cells rather than true CK8/18-negative basal cells. |
Databáze: | OpenAIRE |
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