Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours

Mensdorff‐Pouilly, Silvia von; Gourevitch, M.M.; Kenemans, P.; Verstraeten, A.A.; Litvinov, Sergey V.; Kamp, Gerard J. van; Meijer, Sybren L.; Vermorken, Jan B.; Hilgers, J.

doi:10.1016/0959-8049(96)00048-2

Cited by 122 publications

(84 citation statements)

References 27 publications

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“…To assess the diagnostic accuracy of single antibody versus combined antibody measurements, the average levels of autoantibodies directed against PPIA, PRDX2, FKBP52, and two other previously described tumor-associated antigens, HSP60 (6) and MUC1 (16), were quantified by ELISA in sera from 60 early-stage primary breast cancers, 82 CIS, and 93 healthy controls ( Table 1). All five markers showed individual significant differences between early-stage primary breast cancer and healthy controls, whereas only FKBP52, PPIA, and PRDX2 autoantibodies allowed significant discrimination between CIS and healthy controls ( Table 2; Supplementary Data 2).…”

Section: Resultsmentioning

confidence: 99%

Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women

Desmetz

Bascoul-Mollevi

Rochaix

et al. 2009

Clinical Cancer Research

100

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Purpose: We examined the feasibility of using a panel of autoantibodies to multiple tumor-associated proteins as a method for early detection of breast cancer and, more particularly, carcinoma in situ (CIS). Experimental Design: PPIA, PRDX2, and FKBP52 were identified as early-stage breast cancer autoantigens by proteomic approaches. The seroreactivity of a panel of antibodies consisting of these three antigens and two previously described autoantigens, HSP60 and MUC1, was tested on 235 samples (60 from primary breast cancer patients, 82 from CIS patients, and 93 from healthy controls) with the use of specific ELISAs. FKBP52, PPIA, and PRDX2 mRNA and protein expression levels were evaluated by reverse transcription-PCR and immunohistochemistry in early-stage breast tumors. Results: Three of five autoantibodies, FKBP52, PPIA, and PRDX2, showed significantly increased reactivity in primary breast cancer and CIS compared with healthy controls.When combined, the five markers significantly discriminated primary breast cancer [receiver operating characteristic area under the curve, 0.73; 95% confidence interval (95% CI), 0.60-0.79] and CIS (receiver operating characteristic area under the curve, 0.80; 95% CI, 0.71-0.85) from healthy individuals. Importantly, the receiver operating characteristic^area under the curve value of the autoantibody panel was able to distinguish CIS, including high grades, from healthy controls in women under the age of 50 years (receiver operating characteristic area under the curve, 0.85; 95% CI, 0.61-0.92). Finally, only FKBP52 mRNA and protein levels were found to be increased in CIS and primary breast cancer compared with healthy breast tissue. Conclusions: This autoantibody assay against a panel of five antigens allows for an accurate discrimination between early-stage breast cancer, especially CIS, and healthy individuals. These results could be of interest in detecting early breast cancer as an aid to mammography, especially in women under the age of 50 years with aggressive cancers.

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Section: Resultsmentioning

confidence: 99%

Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women

Desmetz

Bascoul-Mollevi

Rochaix

et al. 2009

Clinical Cancer Research

100

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“…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.…”

Section: Abstract: Muc1; Breast Cancer; Adcc; Nk Cells; Vaccination;mentioning

confidence: 99%

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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“…77), Mucin 1, cell surface associated (MUC1; ref. 78), and NY-ESO-1 (79) were first discovered in patients with breast cancer. In fact, antibodies to HER2/neu (76) have been detected in patients with early-stage breast cancer but their presence has also been detected in other cancers, limiting their use as a diagnostic biomarker for breast cancer alone (28,30,80).…”

Section: Breast Cancermentioning

confidence: 99%

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

Zaenker

Ziman

2013

Cancer Epidemiology, Biomarkers &Amp; Prevention

135

111

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Current diagnostic techniques used for the early detection of cancers are successful but subject to detection bias. A recent focus lies in the development of more accurate diagnostic tools. An increase in serologic autoantibody levels has been shown to precede the development of cancer disease symptoms. Therefore, autoantibody levels in patient blood serum have been proposed as diagnostic biomarkers for early-stage diagnosis of cancers. Their clinical application has, however, been hindered by low sensitivity, specificity, and low predictive value scores. These scores have been shown to improve when panels of multiple diagnostic autoantibody biomarkers are used. A five-marker biomarker panel has been shown to increase the sensitivity of prostate cancer diagnosis to 95% as compared with 12.2% for prostate-specific antigen alone. New potential biomarker panels were also discovered for lung, colon, and stomach cancer diagnosis with sensitivity of 76%, 65.4%, and 50.8%, respectively. Studies in breast and liver cancer, however, seem to favor single markers, namely a-2-HS-glycoprotein and des-g-carboxyprothrombin with sensitivities of 79% and 89% for the early detection of the cancers. The aim of this review is to discuss the relevance of autoantibodies in cancer diagnosis and to outline the current methodologies used in the detection of autoantibodies. The review concludes with a discussion of the autoantibodies currently used in the diagnosis of cancers of the prostate, breast, lung, colon, stomach, and liver. A discussion of the potential future use of autoantibodies as diagnostic cancer biomarkers is also included in this review. Cancer Epidemiol Biomarkers Prev; 22(12); 2161-81. Ó2013 AACR.

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Humoral immune response to polymorphic epithelial mucin (MUC-1) in patients with benign and malignant breast tumours

Cited by 122 publications

References 27 publications

Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women

Identification of a New Panel of Serum Autoantibodies Associated with the Presence of In situ Carcinoma of the Breast in Younger Women

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

Serologic Autoantibodies as Diagnostic Cancer Biomarkers—A Review

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