Clinical and technical evaluation of ACS™BR serum assay of MUC1 gene-derived glycoprotein in breast cancer, and comparison with CA 15-3 assays

Bon, Gijsbert G.; Mensdorff‐Pouilly, Silvia von; Kenemans, P.; Kamp, Gerard J. van; Verstraeten, Rob A.; Hilgers, J.; Meijer, Sybren L.; Vermorken, Jan B.

doi:10.1093/clinchem/43.4.585

Cited by 51 publications

(25 citation statements)

References 13 publications

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“…Secondly, the 13 studies in our analysis used different methods/assays to test CA15-3 and CEA levels, including 11 for CA15-3: MEIA, Abbott AxSYM, ELISA, MyBioSource, Antuos, CIS Bio International, CanAg, Calbiotech, IRMA, CLIA and Bayer, and 8 for CEA: MEIA, Abbott AxSYM, ELISA, Antuos, Quorum, CLIA, Bayer and CanAg. Previous research compared 3 different CA15-3 assay kits (the manual IRMA Centocor and 2 fully automated methods, the ELISA-Boehringer Mannheim-ES300 and the Abbott IMx) and showed that they have different sensitivity and could yield inconsistent results [ 27 , 28 ]. Positive rates of the IRMA CA15-3 did not show any significant variations related to stage, while CA15-3 levels obtained by both ELISA and Abbott assays showed higher values in stage I than in stage II patients [ 27 , 28 ].…”

Section: Discussionmentioning

confidence: 99%

Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) Levels in Breast Cancer Patients: A Meta-Analysis

2016

Med Sci Monit

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BackgroundBreast cancer is the most common malignant cancer in women worldwide. The tumor markers Cancer Antigen 15-3 (CA15-3) and Carcinoembryonic Antigen (CEA) are frequently used for screening and monitoring breast cancer.Material/MethodsWe conducted a meta-analysis of 13 published case-control studies to assess the associations between serum levels of CA15-3 and CEA with breast cancer susceptibility, including 1179 cases and 493 controls. The analyses were performed on malignant tumor and benign tumor, as well as in different subgroups with respect to the patient ethnicities and clinical tumor stages.ResultsThis systematic review and meta-analysis of association studies shows that serum levels of CA15-3 and CEA are potential biomarkers for breast cancer monitoring. When stratified by clinical stage, we noticed that although malignant tumors in all stages show elevated levels of CA15-3, it is greatly associated with the tumor stage, as it increases as breast tumor stage worsens.ConclusionsThis study clarifies the inconsistent conclusions from multiple studies, and provides a precise estimation for clinical utility of 2 important biomarkers, CA15-3 and CEA, in breast cancer monitoring. Thus, our study will shed lights on the prognosis of breast cancer patients.

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Section: Discussionmentioning

confidence: 99%

Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) Levels in Breast Cancer Patients: A Meta-Analysis

2016

Med Sci Monit

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“…In cancer cells, MUC1 is not only overexpressed but also deficiently glycosylated, which leads to the increased exposure of a variable number of immunodominant areas on its peptide core (Burchell and Taylor‐Papadimitriou, 1993). This potentially immunogenic molecule is present in the circulation of carcinoma patients and measurement of its concentration is used to monitor treatment of breast cancer patients (Bon et al , 1997).…”

Section: Peptides and Galnac‐peptidesmentioning

confidence: 99%

Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides andn-acetylgalactosamine (GalNAc) peptides

et al. 2000

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Antibodies (Abs) to MUC1 occur naturally in both healthy subjects and cancer patients and can be induced by MUC1 peptide vaccination. We compared the specificity of natural and induced MUC1 Abs with the objective of defining an effective MUC1 vaccine for active immunotherapy of adenocarcinoma patients. Serum samples, selected out of a screened population of 492 subjects for their high levels of IgG and/or IgM MUC1 Abs, were obtained from 55 control subjects and from 26 breast cancer patients before primary treatment, as well as from 19 breast cancer patients immunized with MUC1 peptides coupled to keyhole limpet hemocyanin (KLH) and mixed with QS‐21. The samples were tested with enzyme‐linked immunoassays for reactivity with (1) overlapping hepta‐ and 20‐mer peptides spanning the MUC1 tandem repeat sequence; (2) two modified 60‐mer peptides with substitutions in the PDTR (PDTA) or in the STAPPA (STAAAA) sequence of each tandem repeat; and (3) four 60‐mer glycopeptides with each 1, 2, 3 and 5 mol N‐acetylgalactosamine (GalNAc) per repeat. More than one minimal epitopic sequence could be defined, indicating that Abs directed to more than one region of the MUC1 peptide core can coexist in one and the same subject. The most frequent minimal epitopic sequence of natural MUC1 IgG and IgM Abs was RPAPGS, followed by PPAHGVT and PDTRP. MUC1 peptide vaccination induced high titers of IgM and IgG Abs predominantly directed, respectively, to the PDTRPAP and the STAPPAHGV sequences of the tandem repeat. Natural MUC1 Abs from breast cancer patients reacted more strongly with the N‐acetylgalactosamine (GalNAc) peptides than with the naked 60‐mer peptide, while reactivity with the GalNAc‐peptides was significantly reduced (2‐tailed p < 0.0001) in the MUC1 IgG and IgM Abs induced by MUC1 peptide vaccination. Whereas in cancer patients glycans appear to participate in epitope conformation, the epitope(s) recognized by MUC1 Abs induced by peptide vaccination are already masked by minimal glycosylation. Therefore, our results indicate that a MUC1 glycopeptide would be a better vaccine than a naked peptide. Int. J. Cancer 86:702–712, 2000. © 2000 Wiley‐Liss, Inc.

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“…In breast cancer patients MUC1 serum levels are used to monitor therapy and for early detection of recurrences. 9,10 Proliferative responses to MUC1 and its tandem-repeat peptides have been demonstrated with peripheral blood mononuclear cells (PBMC) of patients with ovarian adenocarcinoma 11 and MUC1 specific cytotoxic T lymphocytes (CTL) have been isolated from tumor-draining lymph nodes of breast 12 and ovarian 13 cancer patients. In patients with ovarian, breast and pancreatic adenocarcinomas cytotoxic T cells can be induced that are specific for the MUC1 tandem repeat.…”

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Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

et al. 2001

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Key words: MUC1; breast cancer; ADCC; NK cells; vaccination; immunotherapyMUC1 is a transmembrane O-linked glycoprotein present on the apical surface of normal secretory epithelial cells. 1 The extracellular domain of MUC1 consists mainly of a variable number of tandem repeats 2 and it has a cytoplasmatic tail of 69 amino acids. 3 In the vast majority of human adenocarcinomas this protein is over-expressed and hypo-glycosylated 4 exposing an immunodominant repetitive amino acid sequence. The overproduction and secretion of MUC1 is correlated with the progression of breast, 5 ovarian 6,7 and colon 8 carcinoma. In breast cancer patients MUC1 serum levels are used to monitor therapy and for early detection of recurrences. 9,10 Proliferative responses to MUC1 and its tandem-repeat peptides have been demonstrated with peripheral blood mononuclear cells (PBMC) of patients with ovarian adenocarcinoma 11 and MUC1 specific cytotoxic T lymphocytes (CTL) have been isolated from tumor-draining lymph nodes of breast 12 and ovarian 13 cancer patients. In patients with ovarian, breast and pancreatic adenocarcinomas cytotoxic T cells can be induced that are specific for the MUC1 tandem repeat. 14,15 Recognition of MUC1 by T lymphocytes may be due to exposure of the immunogenic PDTRP region of the tandem repeat that is normally not exposed due to extensive O-glycosylation of the peptide core. The cytotoxic action of these T cells has also been described to be MHC-nonrestricted, due to crosslinkage to poorly glycosylated MUC1 tandem repeats on tumor cells. 16 Not only cellular but also humoral responses to MUC1 are found in breast, ovarian, colon and pancreatic carcinomas. [17][18][19] Moreover, the presence of immune-complexed MUC1 in breast cancer patients is related to a favorable disease outcome 20 and survival in early breast cancer patients is favorably influenced by a natural humoral immune response to MUC1. 21 These findings point to MUC1 and its repeat peptide as a target for immunotherapy of carcinomas. One possible approach is the use of MAbs against tumor-associated antigens, 22,23 another the use of tumorassociated antigens such as MUC1 as a vaccine and target for cellular and humoral immune responses.MUC1 MAbs have already been used in a number of vaccination trials as carrier molecule of radioactive elements 24,25 and recently a clinical trial has been set up with unlabeled humanized (Hu)HMFG-1 MAb for adjuvant therapy of breast cancer patients (Dr. D.W. Miles, Guy's Hospital, London). Also active vaccination trials with MUC1 tandem-repeat peptides 26 have been initiated. Recently, in 3 phase I vaccination trials executed by Dr. P.O. Livingston in the Memorial Sloan-Kettering Cancer Center, NY, breast cancer patients with no evidence of disease were repeatedly injected with a 30-mer 27,28 a 33-mer or a 106-mer MUC1 tandem repeat peptide conjugated to KLH plus adjuvant QS-21. In these patients high MUC1 IgG and IgM could be induced. 21 MAbs specific for tumor-associated antigens (TAA) can induce a complement-depende...

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Clinical and technical evaluation of ACS™BR serum assay of MUC1 gene-derived glycoprotein in breast cancer, and comparison with CA 15-3 assays

Cited by 51 publications

References 13 publications

Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) Levels in Breast Cancer Patients: A Meta-Analysis

Assessing Clinical Significance of Serum CA15-3 and Carcinoembryonic Antigen (CEA) Levels in Breast Cancer Patients: A Meta-Analysis

Reactivity of natural and induced human antibodies to MUC1 mucin with MUC1 peptides andn-acetylgalactosamine (GalNAc) peptides

Antibody-dependent cell-mediated cytotoxicity can be induced by MUC1 peptide vaccination of breast cancer patients

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