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

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 ¼ 38) were always concordant for CK5/14 expression. The majority of the CK5/14-positive cases were of histologic grade III (P ¼ 0.0007) and steroid hormone receptor negative (Po0.0001). CK5/14 expression was inversely associated with HER-2 oncogene amplification, but only in the subgroup of estrogen receptornegative tumors (P ¼ 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.

Basal phenotype of ductal carcinoma in situ: recognition and immunohistologic profile

“…Our study confirms and extends the previously reported findings of the basal-like carcinoma immunophenotype. [5][6][7][8]10 In addition, we demonstrate the presence of in situ carcinoma as the likely precursor lesion for invasive basal-like carcinoma.…”

“…This was performed simply to increase the yield of high-grade, ER-negative breast carcinomas, as these are more common in the younger age group. The majority of BRCA-1-associated tumors have the basal phenotype, 8,18,19 but the BRCA-1 status was not available for any of our cases.…”

“…5 The characteristic immunohistologic phenotype of these tumors is the 'triple negative' receptors of estrogen, progesterone and HER-2/neu, while expressing keratins CK5/6, CK14, CK17, vimentin and HER-1. [5][6][7][8][9][10][11] While the invasive basal-like neoplasms are reasonably well characterized morphologically and immunohistochemically, there is little data about the precursor lesion(s) for the entity.…”

Recurrent gross mutations of the PTEN tumor suppressor gene in breast cancers with deficient DSB repair

“…Tissue microarrays containing formalin-fixed paraffin-embedded tissues in replicates from 425 individuals diagnosed with stage II invasive breast cancer but without a significant family history of breast or ovarian cancer were subjected to IHC staining for CK5/14. CK5/14 IHC was performed and scored into CK5/14-positive (defining basal-like status) and CK5/14-negative groups as described 17 . Some of these individuals were evaluated for PTEN protein expression by IHC on whole-mount, formalin-fixed, paraffin-embedded tissue sections, and the tumors were scored as PTEN-positive (PTEN IHC-positive ) or PTEN-loss (PTEN IHC-loss ) relative to normal epithelial, endothelial and/or stromal cells in each tissue section as described 15 .…”

Aquaporin-1-Expression bei invasiven Mammakarzinomen

“…Sie machen 2-18% al ler invasiven Mammakarzinome aus und sind durch einen hohen Malignitätsgrad, das Fehlen von Hormonrezeptoren und HER2/neu, einer häufigen EGFR ("epi dermal growth factor receptor ")Über expression sowie immunphänotypischen Merkmalen basaler bzw. myoepithelialer Brustepithelzellen charakterisiert [7,10,16,19,22]. BLBCs stellen den häufigsten Subtyp bei BRCA1 assoziierten Mamma karzinomen dar [20].…”