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.
Department of Pathology, Seinäjoki Central Hospital, Seinäjoki, Finland. mervi.laakso@epshp.fi
Mervi
M
Laakso
Niklas
N
Loman
Ake
A
Borg
Jorma
J
Isola
D019313:BRCA1 Protein / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000378:metabolism* / Q000473:pathology; D015331:Cohort Studies; D004268:DNA-Binding Proteins; D005260:Female; D016147:Genes, Tumor Suppressor; D018734:Genes, erbB-2; D006801:Humans; D007150:Immunohistochemistry; D007633:Keratins / Q000378:metabolism*; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D010641:Phenotype; D010750:Phosphoproteins / Q000378:metabolism; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins
D019313:BRCA1 Protein; D004268:DNA-Binding Proteins; D007633:Keratins; D010750:Phosphoproteins; D018719:Erb-b2 Receptor Tyrosine Kinases; D015534:Trans-Activators; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; C115051:TP63 protein, human