Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors

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.