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

Laakso, M; Loman, Niklas LU ; Borg, Åke LU and Isola, J (2005) In Modern Pathology 18(10). p.1321-1328
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/... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
immunohistochemistry, HER-2, cytokeratin, BRCA2, basal phenotype, BRCA1, oncogene, progenitor cell
in
Modern Pathology
volume
18
issue
10
pages
1321 - 1328
publisher
Nature Publishing Group
external identifiers
  • wos:000232145600006
  • pmid:15990899
  • scopus:25144516817
ISSN
1530-0285
DOI
10.1038/modpathol.3800456
language
English
LU publication?
yes
id
60793369-481c-446e-ba9e-489cf6fd5746 (old id 223066)
date added to LUP
2007-08-07 15:23:08
date last changed
2017-08-20 04:30:38
@article{60793369-481c-446e-ba9e-489cf6fd5746,
  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 &lt; 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.},
  author       = {Laakso, M and Loman, Niklas and Borg, Åke and Isola, J},
  issn         = {1530-0285},
  keyword      = {immunohistochemistry,HER-2,cytokeratin,BRCA2,basal phenotype,BRCA1,oncogene,progenitor cell},
  language     = {eng},
  number       = {10},
  pages        = {1321--1328},
  publisher    = {Nature Publishing Group},
  series       = {Modern Pathology},
  title        = {Cytokeratin 5/14-positive breast cancer: true basal phenotype confined to BRCA1 tumors},
  url          = {http://dx.doi.org/10.1038/modpathol.3800456},
  volume       = {18},
  year         = {2005},
}