1. Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors
- Author
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Åke Borg, Niklas Loman, Mervi Laakso, and Jorma Isola
- Subjects
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 - Abstract
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.
- Published
- 2005