Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.
ADVANCED SEARCH
Log in
Top
Breast Cancer Research and Treatment
Published in: Breast Cancer Research and Treatment 3/2011

01-02-2011 | Clinical trial

Detection and clinical relevance of early disseminated breast cancer cells depend on their cytokeratin expression pattern

Authors: Katharina E. Effenberger, Elin Borgen, Christine zu Eulenburg, Kai Bartkowiak, Andrea Grosser, Marit Synnestvedt, Rolf Kaaresen, Burkhard Brandt, Jahn M. Nesland, Klaus Pantel, Bjorn Naume

Published in: Breast Cancer Research and Treatment | Issue 3/2011

Login to get access

Abstract

The factors determining the clinical relevance of disseminated tumor cells (DTC) in breast cancer patients are largely unknown. Here we compared the specificity and clinical performance of two antibodies frequently used for DTC detection. Reactivities of antibodies A45-B/B3 (A45) and AE1/AE3 (AE) for selected cytokeratins (CK) were assessed by 2-DE Western Blot analysis. Using these antibodies bone marrow aspirates from 391 breast cancer patients (M0, pT1-3, pN0-3) were screened for the presence of DTC. To obtain prognostic information, patients were followed up over a median of 83 months for time to relapse and 99 months for time to death. Among the analyzed CK, AE detected CK5, CK7, CK8, and CK19, whereas A45 recognized CK7 and CK18. In total, 24 of 391 patients (6.1%) were DTC-positive for A45, and 41 (10.5%) for AE. Although concordance between the two antibodies was 84.4%, overlap among positive cases was only 3.2%. DTC-positivity with AE and A45 was more frequent in patients of higher nodal status (P = 0.019 and P = 0.036, respectively). Nearly all patients with A45-positive DTC had hormone receptor-positive tumors (23/24), while detection of AE-positive DTC was more frequent among hormone receptor negative patients (P = 0.006). Survival analyses of all patients revealed shorter distant disease-free survival (P = 0.039) for patients with A45-positive DTC, whereas the prognostic relevance of AE-positive DTC was restricted to node-positive patients. The clinical utility of immunocytochemical (ICC) DTC detection depends on the anti-CK antibody used, which may reflect the complex CK composition of DTC.
Appendix
Available only for authorised users
Literature
1.
Pantel K, Cote RJ, Fodstad O (1999) Detection and clinical importance of micrometastatic disease. J Natl Cancer Inst 91:1113–1124CrossRefPubMed
2.
Gnant M, Mlineritsch B, Schippinger W et al (2009) Endocrine therapy plus zoledronic acid in premenopausal breast cancer. N Engl J Med 360:679–691CrossRefPubMed
3.
Scher HI, Pantel K (2009) Bone marrow aspiration for disseminated tumor cell detection: a must-have test or is the jury still out? J Clin Oncol 27:1531–1533CrossRefPubMed
4.
Pantel K, Brakenhoff RH, Brandt B (2008) Detection, clinical relevance and specific biological properties of disseminating tumour cells. Nat Rev Cancer 8:329–340CrossRefPubMed
5.
Brugger W, Bross KJ, Glatt M et al (1994) Mobilization of tumor cells and hematopoietic progenitor cells into peripheral blood of patients with solid tumors. Blood 83:636–640PubMed
6.
Bidard FC, Vincent-Salomon A, Gomme S et al (2008) Disseminated tumor cells of breast cancer patients: a strong prognostic factor for distant and local relapse. Clin Cancer Res 14:3306–3311CrossRefPubMed
7.
Zhang XH, Wang Q, Gerald W et al (2009) Latent bone metastasis in breast cancer tied to Src-dependent survival signals. Cancer Cell 16:67–78CrossRefPubMed
8.
Borgen E, Naume B, Nesland JM et al (1999) Standardization of the immunocytochemical detection of cancer cells in BM and blood: I. establishment of objective criteria for the evaluation of immunostained cells. Cytotherapy 1:377–388CrossRefPubMed
9.
Fehm T, Braun S, Muller V et al (2006) A concept for the standardized detection of disseminated tumor cells in bone marrow from patients with primary breast cancer and its clinical implementation. Cancer 107:885–892CrossRefPubMed
10.
Pantel K, Schlimok G, Angstwurm M et al (1994) Methodological analysis of immunocytochemical screening for disseminated epithelial tumor cells in bone marrow. J Hematother 3:165–173PubMed
11.
Fuchs E, Weber K (1994) Intermediate filaments: structure, dynamics, function, and disease. Annu Rev Biochem 63:345–382PubMed
12.
Borgen E, Pantel K, Schlimok G et al (2006) A European interlaboratory testing of three well-known procedures for immunocytochemical detection of epithelial cells in bone marrow. Results from analysis of normal bone marrow. Cytometry B Clin Cytom 70:400–409PubMed
13.
Braun S, Pantel K, Muller P et al (2000) Cytokeratin-positive cells in the bone marrow and survival of patients with stage I, II, or III breast cancer. N Engl J Med 342:525–533CrossRefPubMed
14.
Naume B, Borgen E, Kvalheim G et al (2001) Detection of isolated tumor cells in bone marrow in early-stage breast carcinoma patients: comparison with preoperative clinical parameters and primary tumor characteristics. Clin Cancer Res 7:4122–4129PubMed
15.
Wiedswang G, Borgen E, Karesen R et al (2003) Detection of isolated tumor cells in bone marrow is an independent prognostic factor in breast cancer. J Clin Oncol 21:3469–3478CrossRefPubMed
16.
Willipinski-Stapelfeldt B, Riethdorf S, Assmann V et al (2005) Changes in cytoskeletal protein composition indicative of an epithelial-mesenchymal transition in human micrometastatic and primary breast carcinoma cells. Clin Cancer Res 11:8006–8014CrossRefPubMed
17.
Woelfle U, Sauter G, Santjer S et al (2004) Down-regulated expression of cytokeratin 18 promotes progression of human breast cancer. Clin Cancer Res 10:2670–2674CrossRefPubMed
18.
Mani SA, Guo W, Liao MJ et al (2008) The epithelial-mesenchymal transition generates cells with properties of stem cells. Cell 133:704–715CrossRefPubMed
19.
Kasper M, Stosiek P, Typlt H et al (1987) Histological evaluation of three new monoclonal anti-cytokeratin antibodies. 1. Normal tissues. Eur J Cancer Clin Oncol 23:137–147CrossRefPubMed
20.
Waseem A, Karsten U, Leigh IM et al (2004) Conformational changes in the rod domain of human keratin 8 following heterotypic association with keratin 18 and its implication for filament stability. Biochemistry 43:1283–1295CrossRefPubMed
21.
Woodcock-Mitchell J, Eichner R, Nelson WG et al (1982) Immunolocalization of keratin polypeptides in human epidermis using monoclonal antibodies. J Cell Biol 95:580–588CrossRefPubMed
22.
Sun TT, Tseng SC, Huang AJ et al (1985) Monoclonal antibody studies of mammalian epithelial keratins: a review. Ann N Y Acad Sci 455:307–329CrossRefPubMed
23.
Bartkowiak K, Wieczorek M, Buck F et al (2009) Two-dimensional differential gel electrophoresis of a cell line derived from a breast cancer micrometastasis revealed a stem/progenitor cell protein profile. J Proteome Res 8:2004–2014CrossRefPubMed
24.
McShane LM, Altman DG, Sauerbrei W et al (2005) Reporting recommendations for tumor marker prognostic studies. J Clin Oncol 23:9067–9072CrossRefPubMed
25.
Abd El-Rehim DM, Pinder SE, Paish CE et al (2004) Expression of luminal and basal cytokeratins in human breast carcinoma. J Pathol 203:661–671CrossRefPubMed
26.
van de Rijn M, Perou CM, Tibshirani R et al (2002) Expression of cytokeratins 17 and 5 identifies a group of breast carcinomas with poor clinical outcome. Am J Pathol 161:1991–1996PubMed
27.
Naume B, Wiedswang G, Borgen E et al (2004) The prognostic value of isolated tumor cells in bone marrow in breast cancer patients: evaluation of morphological categories and the number of clinically significant cells. Clin Cancer Res 10:3091–3097CrossRefPubMed
28.
Braun S, Vogl FD, Naume B et al (2005) A pooled analysis of bone marrow micrometastasis in breast cancer. N Engl J Med 353:793–802CrossRefPubMed
29.
Schindlbeck C, Kampik T, Janni W et al (2005) Prognostic relevance of disseminated tumor cells in the bone marrow and biological factors of 265 primary breast carcinomas. Breast Cancer Res 7:R1174–R1185CrossRefPubMed
30.
Slade MJ, Singh A, Smith BM et al (2005) Persistence of bone marrow micrometastases in patients receiving adjuvant therapy for breast cancer: results at 4 years. Int J Cancer 114:94–100CrossRefPubMed
31.
van de Vijver MJ, He YD, van’t Veer LJ et al (2002) A gene-expression signature as a predictor of survival in breast cancer. N Engl J Med 347:1999–2009CrossRefPubMed
32.
Korsching E, Packeisen J, Agelopoulos K et al (2002) Cytogenetic alterations and cytokeratin expression patterns in breast cancer: integrating a new model of breast differentiation into cytogenetic pathways of breast carcinogenesis. Lab Invest 82:1525–1533PubMed
33.
Korsching E, Packeisen J, Helms MW et al (2004) Deciphering a subgroup of breast carcinomas with putative progression of grade during carcinogenesis revealed by comparative genomic hybridisation (CGH) and immunohistochemistry. Br J Cancer 90:1422–1428CrossRefPubMed
34.
Naume B, Zhao X, Synnestvedt M et al (2007) Presence of bone marrow micrometastasis is associated with different recurrence risk within molecular subtypes of breast cancer. Mol Oncol 1:160–171CrossRefPubMed
35.
Polyak K, Weinberg RA (2009) Transitions between epithelial and mesenchymal states: acquisition of malignant and stem cell traits. Nat Rev Cancer 9:265–273CrossRefPubMed
Metadata
Title
Detection and clinical relevance of early disseminated breast cancer cells depend on their cytokeratin expression pattern
Authors
Katharina E. Effenberger
Elin Borgen
Christine zu Eulenburg
Kai Bartkowiak
Andrea Grosser
Marit Synnestvedt
Rolf Kaaresen
Burkhard Brandt
Jahn M. Nesland
Klaus Pantel
Bjorn Naume
Publication date
01-02-2011
Publisher
Springer US
Published in
Breast Cancer Research and Treatment / Issue 3/2011
Print ISSN: 0167-6806
Electronic ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-010-0911-2

Other articles of this Issue 3/2011

Breast Cancer Research and Treatment 3/2011 Go to the issue

Preclinical Study

Tumor–stroma ratio in the primary tumor is a prognostic factor in early breast cancer patients, especially in triple-negative carcinoma patients

Brief Report

Two novel variants in the 3′UTR of the BRCA1 gene in familial breast and/or ovarian cancer

Preclinical study

Inhibition of focal adhesion kinase suppresses the adverse phenotype of endocrine-resistant breast cancer cells and improves endocrine response in endocrine-sensitive cells

Clinical trial

Evaluation of estrogen and progesterone receptors in non-neoplastic breast tissue of women of reproductive age exposed to tamoxifen and raloxifene: a randomized, double-blind study

Editorial

Changes in leadership of breast cancer research and treatment

Epidemiology

RAD51 135G/C polymorphism and breast cancer risk: a meta-analysis from 21 studies
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras
Prof. Fabrice Barlesi
Developed by: Springer Medicine
Image Credits