Basal cell-specific and hyperproliferation-related keratins in human breast cancer. Am J Pathol

Department of Pathology, University Hospital, Nijmegen, The Netherlands.
American Journal Of Pathology (Impact Factor: 4.6). 04/1991; 138(3):751-63.
Source: PubMed

ABSTRACT In normal breast tissue and in noninvasive breast carcinomas, various keratin-14 antibodies were reactive predominantly with the basal/myoepithelial cell layer, although mainly in terminal and larger ducts luminal cells sometimes also were stained. A similar reaction pattern was found with an antibody directed against keratin 17, although this antibody was more often found negative than keratin 14 in the pre-existing myoepithelial cells in intraductal carcinomas. Furthermore antibodies reactive with hyperproliferation-related keratins 6 and 16 were used. One of these (LL025) was completely negative in normal breast tissue and noninvasive breast carcinomas. However 10% of the invasive carcinomas were diffusely or focally positive with this latter antibody, while in 18 of 115 cases of invasive breast carcinomas studied, a basal cell phenotype was detected. A relatively high concordance was found between the carcinomas immunostaining with the basal cell and the hyperproliferation-related keratins, but not between these markers and the proliferation marker Ki-67. This supports the conclusion that basal cells in breast cancer may show extensive proliferation, and that absence of Ki-67 staining does not mean that (tumor) cells are not proliferating.

Download full-text


Available from: Ellen Birgitte Lane, Aug 25, 2015
  • Source
    • "The relative high abundances of liver cytokeratins 8 and 18 reflect the presence of hepatocytes [5]. Similarly, in mammary samples cytokeratins 7, 8, 18 and 19 are characteristic of the milk synthesizing luminal epithelia while cytokeratins 5, 14 and 17 are typical of myoepithelial cells [6]. Also, some enzymes are generally not detected on 2D gels, either due to low abundance, hydrophobic character, or co-distribution with more abundant proteins that produce prominent ions during mass spectrometry. "
    [Show abstract] [Hide abstract]
    ABSTRACT: The liver and the mammary gland have complementary metabolic roles during lactation. Glucose synthesized by the liver is released into the circulation and is taken up by the mammary gland where major metabolic products of glucose include milk sugar (lactose) and the glycerol backbone of milk fat (triglycerides). Hepatic synthesis of glucose is often accompanied by β-oxidation in that organ to provide energy for glucose synthesis, while mammary gland synthesizes rather than oxidizes fat during lactation. We have therefore compared enzyme abundances between the liver and mammary gland of lactating Friesian cows where metabolic output is well established. Quantitative differences in protein amount were assessed using two-dimensional differential in-gel electrophoresis. As predicted, the abundances of enzymes catalysing gluconeogenesis and β-oxidation were greatest in the liver, and enzyme abundances in mammary tissue were consistent with fat synthesis rather than β-oxidation.
    Journal of proteomics 04/2012; 75(14):4429-35. DOI:10.1016/j.jprot.2012.04.019 · 3.93 Impact Factor
  • Source
    • "Basal-like breast cancers derive their name from their characteristic expression of basal and myoepithelial markers such as cytokeratins (CK) 5, 14 and 17 (Jarasch et al, 1988; Wetzels et al, 1991). These tumours account for up to 15% of all invasive breast cancers (van de Rijn et al, 2002; Abd El-Rehim et al, 2004; Nielsen et al, 2004; Matos et al, 2005). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Basal-like tumours account for 15% of invasive breast carcinomas and are associated with a poorer prognosis and resistance to therapy. We hypothesised that this aggressive phenotype is because of an intrinsically elevated hypoxic response. Microarrayed tumours from 188 patients were stained for hypoxia-inducible factor (HIF)-1alpha, prolyl hydroxylase (PHD)1, PHD2, PHD3 and factor inhibiting HIF (FIH)-1, and carbonic anhydrase (CA) IX stained in 456 breast tumours. Tumour subtypes were correlated with standard clincopathological parameters as well as hypoxic markers. Out of 456 tumours 62 (14%) tumours were basal-like. These tumours were positively correlated with high tumour grade (P<0.001) and were associated with a significantly worse disease-free survival compared with luminal tumours (P<0.001). Fifty percent of basal-like tumours expressed HIF-1alpha, and more than half expressed at least one of the PHD enzymes and FIH-1. Basal-like tumours were nine times more likely to be associated with CAIX expression (P<0.001) in a multivariate analysis. Carbonic anhydrase IX expression was positively correlated with tumour size (P=0.005), tumour grade (P<0.001) and oestrogen receptor (ER) negativity (P<0.001). Patients with any CAIX-positive breast tumour phenotype and in the basal tumour group had a significantly worse prognosis than CAIX-negative tumours when treated with chemotherapy (P<0.001 and P=0.03, respectively). The association between basal phenotype and CAIX suggests that the more aggressive behaviour of these tumours is partly due to an enhanced hypoxic response. Further, the association with chemoresistance in CAIX-positive breast tumours and basal-like tumours in particular raises the possibility that targeted therapy against HIF pathway or downstream genes such as CAs may be an approach to investigate for these patients.
    British Journal of Cancer 01/2009; 100(2):405-11. DOI:10.1038/sj.bjc.6604844 · 4.82 Impact Factor
  • Source
    • "Anti-cytokeratin 14 antibody (Chemicon, MAB3232) is a mouse monoclonal IgG raised by immunizing purified proteins from epithelial cells, and its specificity has been confirmed by Western blotting of human buccal epithelial cell extracts recognizing 50 kD proteins (Wetzels et al., 1991). "
    [Show abstract] [Hide abstract]
    ABSTRACT: Vertebrate taste buds undergo continual cell turnover. To understand how the gustatory progenitor cells in the stratified lingual epithelium migrate and differentiate into different types of mature taste cells, we sought to identify genes that were selectively expressed in taste cells at different maturation stages. Here we report the expression of the voltage-gated potassium channel KCNQ1 in mammalian taste buds of mouse, rat, and human. Immunohistochemistry and nuclear staining showed that nearly all rodent and human taste cells express this channel. Double immunostaining with antibodies against type II and III taste cell markers validated the presence of KCNQ1 in these two types of cells. Co-localization studies with cytokeratin 14 indicated that KCNQ1 is also expressed in type IV basal precursor cells. Null mutation of the kcnq1 gene in mouse, however, did not alter the gross structure of taste buds or the expression of taste signaling molecules. Behavioral assays showed that the mutant mice display reduced preference to some umami substances, but not to any other taste compounds tested. Gustatory nerve recordings, however, were unable to detect any significant change in the integrated nerve responses of the mutant mice to umami stimuli. These results suggest that although it is expressed in nearly all taste bud cells, the function of KCNQ1 is not required for gross taste bud development or peripheral taste transduction pathways, and the reduced preference of kcnq1-null mice in the behavioral assays may be attributable to the deficiency in the central nervous system or other organs.
    The Journal of Comparative Neurology 01/2009; 512(3):384-98. DOI:10.1002/cne.21899 · 3.51 Impact Factor
Show more