Differential diagnosis of benign epithelialproliferations and carcinomas of the breast using antibodies to cytokeratins

Jarasch, Ernst-Dieter; Nagle, Ray B.; Kaufmann, M.; Maurer, Clemens; Böcker, W.

doi:10.1016/s0046-8177(88)80520-3

Cited by 118 publications

(64 citation statements)

References 24 publications

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“…[22][23][24][25] The majority of these studies considered breast lesions to be a homogeneous disease with respect to the cellular composition of the growth fraction. In contrast to this view, our previous results, [8][9][10][11][12] in line with findings of others, 26 indicated that different cell types are involved in the development and progression of benign proliferative breast diseases on the one hand and of premalignant and malignant breast diseases on the other hand. In addition to the well-known glandular (CK8/18/ 19 þ ) and myoepithelial (smooth muscle actin þ ) cells, a third cell type could clearly be identified in the breast parenchyma, which is characterized by the expression of basal-type keratins CK5/14 only.…”

Section: Discussionsupporting

confidence: 86%

“…This cell type expresses basal cell-specific keratins CK5/14 and is located both in the basal/parabasal layers and in the luminal compartment. 4,[8][9][10][11] These cells were first interpreted as being myoepithelial cells, later they were proposed to represent progenitor cells in the human breast. 12 Most recently, we provided evidence by double-immunofluorescence labeling and Western blot analysis for the existence of CK5/14 þ progenitor cells within the breast epithelium, which have the property to differentiate into glandular and myoepithelial cells via intermediary hybrid progenies.…”

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Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases

et al. 2004

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The aim of the present study was to explore cell biological characteristics of normal breast, benign proliferative breast diseases and noninvasive breast malignancies based on the recently published adult progenitor cell concept from our group. Here, we investigated the proliferative activity of CK5/14 þ , CK8/18/19 þ and a-smooth muscle actin þ cellular phenotypes encountered in normal mammary gland, in a series of usual ductal hyperplasias and early malignant breast diseases, such as atypical ductal and lobular hyperplasias, as well as ductal and lobular in situ carcinomas. Immunohistochemical double labeling was performed on frozen sections from diagnostic breast biopsies by using antibodies to basal cytokeratins (CK5/14), glandular cytokeratins (CK8/18/19), smooth muscle actin and the Ki-67 antigen (MIB1). Normal breast tissues and usual ductal hyperplasias were characterized by a heterogeneous cellular composition of the growth fraction. The proliferative cell compartment consisted of CK8/18/19 þ glandular and, in a variable proportion, CK5/14 þ progenitor phenotypes. In contrast, noninvasive breast malignancies were composed of a monotonous proliferation of CK 8/18/19 þ neoplastic glandular cells. These findings indicate a significant role of progenitor cells in the development of benign proliferative breast diseases and lend support to the view that malignant transformation in the human breast usually occurs in a cell committed to the glandular lineage. Our results provide cell kinetic support to the functional progenitor cell hypothesis, and we propose this concept as an operative model for understanding benign proliferative and malignant breast diseases.

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Section: Discussionsupporting

confidence: 86%

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confidence: 99%

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases

et al. 2004

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“…In the assessment of atypical papillary lesions (ADH/DCIS involving benign intraductal papilloma or papillary DCIS), immunohistochemical evaluation of the expression of HMWCK is a valuable adjunct, in which benign papillary lesions exhibit strong, mosaic reactivity throughout the lesion in 88% to 100% of cases, and atypical papillary lesions are nonreactive, indicating a clonal proliferation of luminal epithelial cells in 80% to 100% of cases. 19,20,68,69,[81][82][83] Hormonal receptors, such as ER, may have additional value; in general, benign lesions show only scattered staining, whereas atypical papillary lesions are usually diffusely positive. 77,78,84,85 In addition, neuroendocrine markers, such as synaptophysin and chromogranin, have been reported to be positive in most solid papillary CAs and negative in benign and atypical papillary lesions.…”

Section: The Evaluation Of Papillary Lesionsmentioning

confidence: 99%

Application of Immunohistochemistry in Breast Pathology: A Review and Update

Liu

2014

Archives of Pathology &Amp; Laboratory Medicine

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Context.-Immunohistochemistry is a valuable tool in routine breast pathology, used for both diagnostic and prognostic parameters. The diagnostic immunomarkers are the scope of this review. Most breast lesions can be diagnosed on routine hematoxylin-eosin sections; however, in several scenarios, such as morphologically equivocal cases or metastatic tumors of unknown primary, the appropriate application of immunohistochemistry adds true value in reaching an accurate diagnosis.Objective.-To evaluate the diagnostic utility of the most commonly studied immunomarkers in the field of breast pathology by review of the literature, using the database of indexed articles in PubMed (US National Library of Medicine, Bethesda, Maryland) from 1976 to 2013.Data Sources.-Literature review, and author's research data and personal practice experience.Conclusions.-The appropriate use of immunohistochemistry by applying a panel of immunomarkers and using a standardized technical and interpretational method will complement the morphologic assessment and aid in the accurate classification of difficult breast lesions and the identification of metastasis from a breast primary.

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“…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).…”

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The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy

et al. 2009

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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)-1a, 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 (Po0.001) and were associated with a significantly worse disease-free survival compared with luminal tumours (Po0.001). Fifty percent of basal-like tumours expressed HIF-1a, 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 (Po0.001) in a multivariate analysis. Carbonic anhydrase IX expression was positively correlated with tumour size (P ¼ 0.005), tumour grade (Po0.001) and oestrogen receptor (ER) negativity (Po0.001). 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 (Po0.001 and P ¼ 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.

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Differential diagnosis of benign epithelialproliferations and carcinomas of the breast using antibodies to cytokeratins

Cited by 118 publications

References 24 publications

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases

Different proliferative activity of the glandular and myoepithelial lineages in benign proliferative and early malignant breast diseases

Application of Immunohistochemistry in Breast Pathology: A Review and Update

The key hypoxia regulated gene CAIX is upregulated in basal-like breast tumours and is associated with resistance to chemotherapy

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