Skip to main content
Top
Published in: Breast Cancer 6/2015

01-11-2015 | Original Article

Detection of breast cancer from blood through analysis of lymphocyte fluorescent intensity using MUC1 antigen

Authors: Ayelet Armon-Omer, Amram Hadary, Georgette Hilu, Bat-el Tayar, Tali Keren, Adi Sharabi-Nov, Amitai Bickel, Ofer Klein

Published in: Breast Cancer | Issue 6/2015

Login to get access

Abstract

Background

Sensitive and reliable early diagnostic markers for breast cancer (BC) are still unavailable today. In this work, we proposed a new complementary method for detection of BC. This method is based on an observation that lymphocytes re-exposed in vitro to antigenic stimulation express cytoplasmic changes.

Methods

In the new protocol, we recorded changes in the fluorescence intensity of light emitted from lymphocytes obtained from females with and without BC after stimulation with MUC1 antigen utilized flow cytometry.

Results

Out of 55 BC patients tested, 46 were correctly diagnosed. Of 73 controls, 55 were correctly identified as healthy subjects. The sensitivity of the test was 84 %; the specificity was 75 %.

Conclusion

These results suggest a potentially valuable method for detection of BC. The clinical importance of this procedure relies on the ability to screen populations for BC with widely available flow cytometry by a relatively fast, accurate, and economical procedure. Another potential benefit would be identification of candidates for vaccination as a primary or secondary preventive measure.
Literature
1.
go back to reference Heyderman E, Steele K, Ormerod MG. A new antigen on the epithelial membrane: its immunoperoxidase localisation in normal and neoplastic tissue. J Clin Pathol. 1979;32:35–9.PubMedCentralCrossRefPubMed Heyderman E, Steele K, Ormerod MG. A new antigen on the epithelial membrane: its immunoperoxidase localisation in normal and neoplastic tissue. J Clin Pathol. 1979;32:35–9.PubMedCentralCrossRefPubMed
2.
go back to reference Singh R, Bandyopadhyay D. MUC1: a target molecule for cancer therapy. Cancer Biol Ther. 2007;6:481–6.CrossRefPubMed Singh R, Bandyopadhyay D. MUC1: a target molecule for cancer therapy. Cancer Biol Ther. 2007;6:481–6.CrossRefPubMed
3.
go back to reference Mukhopadhyay P, Chakraborty S, Ponnusamy MP, Lakshmanan I, Jain M, Batra SK. Mucins in the pathogenesis of breast cancer: implications in diagnosis, prognosis and therapy. Biochim Biophys Acta. 2011;1815:224–40.PubMedCentralPubMed Mukhopadhyay P, Chakraborty S, Ponnusamy MP, Lakshmanan I, Jain M, Batra SK. Mucins in the pathogenesis of breast cancer: implications in diagnosis, prognosis and therapy. Biochim Biophys Acta. 2011;1815:224–40.PubMedCentralPubMed
5.
go back to reference Kufe D, Inghirami G, Abe M, Hayes D, Justi-Wheeler H, Schlom J. Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma. 1984;3:223–32.CrossRefPubMed Kufe D, Inghirami G, Abe M, Hayes D, Justi-Wheeler H, Schlom J. Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma. 1984;3:223–32.CrossRefPubMed
6.
go back to reference Levitin F, Stern O, Weiss M, Gil-Henn C, Ziv R, Prokocimer Z, et al. The MUC1 SEA module is a self-cleaving domain. J Biol Chem. 2005;280:33374–86.CrossRefPubMed Levitin F, Stern O, Weiss M, Gil-Henn C, Ziv R, Prokocimer Z, et al. The MUC1 SEA module is a self-cleaving domain. J Biol Chem. 2005;280:33374–86.CrossRefPubMed
7.
go back to reference Mizejewski GJ. Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor. Tumour Biol. 2013;34(3):1317–1336. Mizejewski GJ. Review of the adenocarcinoma cell surface receptor for human alpha-fetoprotein; proposed identification of a widespread mucin as the tumor cell receptor. Tumour Biol. 2013;34(3):1317–1336.
8.
go back to reference Hattrup CL, Bradley JM, Kotlarczyk KL, Madsen CS, Hentz JG, Marler RJ, et al. The MUC1 cytoplasmic tail and tandem repeat domains contribute to mammary oncogenesis in FVB mice. Breast Cancer (Auckl). 2008;1:57–63. Hattrup CL, Bradley JM, Kotlarczyk KL, Madsen CS, Hentz JG, Marler RJ, et al. The MUC1 cytoplasmic tail and tandem repeat domains contribute to mammary oncogenesis in FVB mice. Breast Cancer (Auckl). 2008;1:57–63.
9.
go back to reference Burchell J, Taylor-Papadimitriou J. Effect of modification of carbohydrate side chains on the reactivity of antibodies with core-protein epitopes of the MUC1 gene product. Epithel Cell Biol. 1993;2:155–62. Burchell J, Taylor-Papadimitriou J. Effect of modification of carbohydrate side chains on the reactivity of antibodies with core-protein epitopes of the MUC1 gene product. Epithel Cell Biol. 1993;2:155–62.
10.
go back to reference Keshaviah A, Dellapasqua S, Rotmensz N, Lindtner J, Crivellari D, Collins J, et al. CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol. 2007;18:701–8.CrossRefPubMed Keshaviah A, Dellapasqua S, Rotmensz N, Lindtner J, Crivellari D, Collins J, et al. CA15-3 and alkaline phosphatase as predictors for breast cancer recurrence: a combined analysis of seven International Breast Cancer Study Group trials. Ann Oncol. 2007;18:701–8.CrossRefPubMed
11.
go back to reference Cercek L, Cercek B. Application of the phenomenon of changes in the structuredness of cytoplasmic matrix (SCM) in the diagnosis of malignant disorders: a review. Eur J Cancer. 1977;13:903–15.CrossRefPubMed Cercek L, Cercek B. Application of the phenomenon of changes in the structuredness of cytoplasmic matrix (SCM) in the diagnosis of malignant disorders: a review. Eur J Cancer. 1977;13:903–15.CrossRefPubMed
12.
go back to reference Klein O, Linn S, Davidson C, Hadary A, Shukha A, Zidan J, et al. Early detection of malignant process in benign lesions of breast tumor by measurements of changes in structuredness of cytoplasmic matrix in circulating lymphocytes (SCM test) reinduced in vitro by specific tumor antigen. Breast. 2002;11:478–83.CrossRefPubMed Klein O, Linn S, Davidson C, Hadary A, Shukha A, Zidan J, et al. Early detection of malignant process in benign lesions of breast tumor by measurements of changes in structuredness of cytoplasmic matrix in circulating lymphocytes (SCM test) reinduced in vitro by specific tumor antigen. Breast. 2002;11:478–83.CrossRefPubMed
13.
go back to reference Smorodinsky N, Weiss M, Hartmann ML, Baruch A, Harness E, Yaakobovitz M, et al. Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies. Biochem Biophys Res Commun. 1996;228:115–21.CrossRefPubMed Smorodinsky N, Weiss M, Hartmann ML, Baruch A, Harness E, Yaakobovitz M, et al. Detection of a secreted MUC1/SEC protein by MUC1 isoform specific monoclonal antibodies. Biochem Biophys Res Commun. 1996;228:115–21.CrossRefPubMed
14.
go back to reference Klein O, Lin S, Embon O, Sazbon A, Zidan J, Kook AI. An approach for high sensitivity detection of prostate cancer by analysis of changes in structuredness of the cytoplasmic matrix of lymphocytes specifically induced by PSA-ACT. J Urol. 1999;161:1994–6.CrossRefPubMed Klein O, Lin S, Embon O, Sazbon A, Zidan J, Kook AI. An approach for high sensitivity detection of prostate cancer by analysis of changes in structuredness of the cytoplasmic matrix of lymphocytes specifically induced by PSA-ACT. J Urol. 1999;161:1994–6.CrossRefPubMed
15.
16.
go back to reference Zurgil N, Deutsch M, Tirosh R, Brodie C. Indication that intracellular fluorescence polarization of T lymphocytes is cell cycle dependent. Cell Struct Funct. 1996;21:271–6.CrossRefPubMed Zurgil N, Deutsch M, Tirosh R, Brodie C. Indication that intracellular fluorescence polarization of T lymphocytes is cell cycle dependent. Cell Struct Funct. 1996;21:271–6.CrossRefPubMed
17.
go back to reference Maecker HT, Moon J, Bhatia S, Ghanekar SA, Maino VC, Payne JK, et al. Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT. BMC Immunol. 2005;6:17.PubMedCentralCrossRefPubMed Maecker HT, Moon J, Bhatia S, Ghanekar SA, Maino VC, Payne JK, et al. Impact of cryopreservation on tetramer, cytokine flow cytometry, and ELISPOT. BMC Immunol. 2005;6:17.PubMedCentralCrossRefPubMed
18.
go back to reference Kurebayashi J, Nishimura R, Tanaka K, Kohno N, Kurosumi M, Moriya T, et al. Significance of serum tumor markers in monitoring advanced breast cancer patients treated with systemic therapy: a prospective study. Breast Cancer. 2004;11(4):389–95.CrossRefPubMed Kurebayashi J, Nishimura R, Tanaka K, Kohno N, Kurosumi M, Moriya T, et al. Significance of serum tumor markers in monitoring advanced breast cancer patients treated with systemic therapy: a prospective study. Breast Cancer. 2004;11(4):389–95.CrossRefPubMed
19.
go back to reference Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.CrossRefPubMed Harris L, Fritsche H, Mennel R, Norton L, Ravdin P, Taube S, et al. American Society of Clinical Oncology 2007 update of recommendations for the use of tumor markers in breast cancer. J Clin Oncol. 2007;25:5287–312.CrossRefPubMed
20.
go back to reference Agrawal B, Krantz MJ, Reddish MA, Longenecker BM. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2. Nat Med. 1998;4:43–9.CrossRefPubMed Agrawal B, Krantz MJ, Reddish MA, Longenecker BM. Cancer-associated MUC1 mucin inhibits human T-cell proliferation, which is reversible by IL-2. Nat Med. 1998;4:43–9.CrossRefPubMed
21.
go back to reference Deutsch M, Kaufman M, Shapiro H, Zurgil N. Analysis of enzyme kinetics in individual living cells utilizing fluorescence intensity and polarization measurements. Cytometry. 2000;39:36–44.CrossRefPubMed Deutsch M, Kaufman M, Shapiro H, Zurgil N. Analysis of enzyme kinetics in individual living cells utilizing fluorescence intensity and polarization measurements. Cytometry. 2000;39:36–44.CrossRefPubMed
22.
go back to reference Afrimzon E, Zurgil N, Shafran Y, Sandbank J, Orda R, Lalchuk S, et al. Monitoring of intracellular enzyme kinetic characteristics of peripheral mononuclear cells in breast cancer patients. Cancer Epidemiol Biomark Prev. 2004;13:235–41.CrossRef Afrimzon E, Zurgil N, Shafran Y, Sandbank J, Orda R, Lalchuk S, et al. Monitoring of intracellular enzyme kinetic characteristics of peripheral mononuclear cells in breast cancer patients. Cancer Epidemiol Biomark Prev. 2004;13:235–41.CrossRef
23.
go back to reference Rabassa ME, Croce MV, Pereyra A, Segal-Eiras A. MUC1 expression and anti-MUC1 serum immune response in head and neck squamous cell carcinoma (HNSCC): a multivariate analysis. BMC Cancer. 2006;6:253.PubMedCentralCrossRefPubMed Rabassa ME, Croce MV, Pereyra A, Segal-Eiras A. MUC1 expression and anti-MUC1 serum immune response in head and neck squamous cell carcinoma (HNSCC): a multivariate analysis. BMC Cancer. 2006;6:253.PubMedCentralCrossRefPubMed
Metadata
Title
Detection of breast cancer from blood through analysis of lymphocyte fluorescent intensity using MUC1 antigen
Authors
Ayelet Armon-Omer
Amram Hadary
Georgette Hilu
Bat-el Tayar
Tali Keren
Adi Sharabi-Nov
Amitai Bickel
Ofer Klein
Publication date
01-11-2015
Publisher
Springer Japan
Published in
Breast Cancer / Issue 6/2015
Print ISSN: 1340-6868
Electronic ISSN: 1880-4233
DOI
https://doi.org/10.1007/s12282-014-0529-z

Other articles of this Issue 6/2015

Breast Cancer 6/2015 Go to the issue
Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

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