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Erschienen in: Breast Cancer Research and Treatment 2/2018

02.02.2018 | Clinical trial

Cross-reactivity between MUC1 antigen and MCA: false elevation of serum CA 15-3 level in pregnant and lactating women by Ma695–Ma552-based assay

verfasst von: Guangshu Liang, Xuqian Fang, Xiaoyi Lin, Xiaojing Feng, Huangying Lu, Yinglei Wan, Zhidong Gu

Erschienen in: Breast Cancer Research and Treatment | Ausgabe 2/2018

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Abstract

Purpose

Cancer antigen 153 (CA 15-3) is one of the most commonly used biomarkers of breast cancer. However, elevated CA 15-3 is reported in pregnant and lactating women more frequently on Beckman DxI 800 immunoassay system (Ma695–Ma552 antibody pair) than on Abbott ARCHITECT system (115D8–DF3 antibody pair) in laboratory methodological evaluation. We conducted this study in order to figure out the reason behind this phenomenon.

Methods

Serum CA 15-3 concentration was analyzed in 426 subjects, including 180 patients with breast cancer, 121 patients with benign breast disease, and 125 healthy volunteers (45 pregnant and 80 non-pregnant women). CA 15-3 assay was further validated using another cohort of 112 pregnant or postpartum women. Immunological cross reaction was analyzed by Western blotting and immunoprecipitation.

Results

The serum CA 15-3 level was abnormally higher in almost 95% of the pregnant and lactating women detected using Ma695–Ma552 antibody pair (median: 71.4 U/mL) than that detected using 115D8–DF3 antibody pair (median: 16.5 U/mL). Western blotting and immunoprecipitation indicated that such a significant difference was mainly due to the cross reaction between monoclonal antibody Ma552 and mucin-like carcinoma-associated antigen (MCA).

Conclusions

The CA 15-3 assay using 115D8–DF3 antibody pair is more suitable for monitoring therapy in pregnancy-associated breast cancer.
Literatur
1.
Zurück zum Zitat Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRefPubMed Torre LA, Bray F, Siegel RL et al (2015) Global cancer statistics, 2012. CA Cancer J Clin 65:87–108CrossRefPubMed
2.
4.
Zurück zum Zitat Slev PR, Rawlins ML, Roberts WL (2006) Performance characteristics of seven automated CA 15-3 assays. Am J Clin Pathol 125:752–757CrossRefPubMed Slev PR, Rawlins ML, Roberts WL (2006) Performance characteristics of seven automated CA 15-3 assays. Am J Clin Pathol 125:752–757CrossRefPubMed
5.
Zurück zum Zitat Molina R, Gion M, Gressner A et al (2008) Alternative antibody for the detection of CA15-3 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access BR Monitor assay on the UniCel Dxl 800 Immunoassay System. Clin Chem Lab Med 46:612–622CrossRefPubMed Molina R, Gion M, Gressner A et al (2008) Alternative antibody for the detection of CA15-3 antigen: a European multicenter study for the evaluation of the analytical and clinical performance of the Access BR Monitor assay on the UniCel Dxl 800 Immunoassay System. Clin Chem Lab Med 46:612–622CrossRefPubMed
6.
Zurück zum Zitat Ho SB, Niehans GA, Lyftogt C et al (1993) Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res 53:641–651PubMed Ho SB, Niehans GA, Lyftogt C et al (1993) Heterogeneity of mucin gene expression in normal and neoplastic tissues. Cancer Res 53:641–651PubMed
7.
Zurück zum Zitat Behera SK, Praharaj AB, Dehury B et al (2015) Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases. Glycoconj J 32:575–613CrossRefPubMed Behera SK, Praharaj AB, Dehury B et al (2015) Exploring the role and diversity of mucins in health and disease with special insight into non-communicable diseases. Glycoconj J 32:575–613CrossRefPubMed
8.
Zurück zum Zitat Ho SB, Kim YS (1991) Carbohydrate antigens on cancer-associated mucin-like molecules. Semin Cancer Biol 2:389–400PubMed Ho SB, Kim YS (1991) Carbohydrate antigens on cancer-associated mucin-like molecules. Semin Cancer Biol 2:389–400PubMed
9.
10.
Zurück zum Zitat Stahli C, Caravatti M, Aeschbacher M et al (1988) Mucin-like carcinoma-associated antigen defined by three monoclonal antibodies against different epitopes. Cancer Res 48:6799–6802PubMed Stahli C, Caravatti M, Aeschbacher M et al (1988) Mucin-like carcinoma-associated antigen defined by three monoclonal antibodies against different epitopes. Cancer Res 48:6799–6802PubMed
11.
Zurück zum Zitat Zenklusen HR, Stahli C, Gudat F et al (1988) The immunohistochemical reactivity of a new anti-epithelial monoclonal antibody (MAb b-12) against breast carcinoma and other normal and neoplastic human tissues. Virchows Arch A Pathol Anat Histopathol 413:3–10CrossRefPubMed Zenklusen HR, Stahli C, Gudat F et al (1988) The immunohistochemical reactivity of a new anti-epithelial monoclonal antibody (MAb b-12) against breast carcinoma and other normal and neoplastic human tissues. Virchows Arch A Pathol Anat Histopathol 413:3–10CrossRefPubMed
12.
Zurück zum Zitat Giannaki G, Sarandakou A, Rizos D et al (2002) Mucin-like carcinoma-associated antigen in paired serum and breast milk samples of lactating mothers and sera of their neonates in the early postpartum period. Eur J Obstet Gynecol Reprod Biol 105:120–123CrossRefPubMed Giannaki G, Sarandakou A, Rizos D et al (2002) Mucin-like carcinoma-associated antigen in paired serum and breast milk samples of lactating mothers and sera of their neonates in the early postpartum period. Eur J Obstet Gynecol Reprod Biol 105:120–123CrossRefPubMed
13.
Zurück zum Zitat Sarandakou A, Rizos D, Botsis D et al (2001) Mucin-like carcinoma-associated antigen (MCA) during normal pregnancy. Eur J Obstet Gynecol Reprod Biol 96:51–54CrossRefPubMed Sarandakou A, Rizos D, Botsis D et al (2001) Mucin-like carcinoma-associated antigen (MCA) during normal pregnancy. Eur J Obstet Gynecol Reprod Biol 96:51–54CrossRefPubMed
14.
Zurück zum Zitat Bieglmayer C, Szepesi T, Neunteufel W et al (1989) MCA, a monoclonal-antibody-defined breast-tumor-associated antigen and its relation to CA 15.3. Tumour Biol 10:232–242CrossRefPubMed Bieglmayer C, Szepesi T, Neunteufel W et al (1989) MCA, a monoclonal-antibody-defined breast-tumor-associated antigen and its relation to CA 15.3. Tumour Biol 10:232–242CrossRefPubMed
15.
Zurück zum Zitat Sarandakou A, Protonotariou E, Rizos D (2007) Tumor markers in biological fluids associated with pregnancy. Crit Rev Clin Lab Sci 44:151–178CrossRefPubMed Sarandakou A, Protonotariou E, Rizos D (2007) Tumor markers in biological fluids associated with pregnancy. Crit Rev Clin Lab Sci 44:151–178CrossRefPubMed
16.
Zurück zum Zitat Price MR, Rye PD, Petrakou E et al (1998) Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996. Tumour Biol 19 Suppl 1:1-20 Price MR, Rye PD, Petrakou E et al (1998) Summary report on the ISOBM TD-4 Workshop: analysis of 56 monoclonal antibodies against the MUC1 mucin. San Diego, Calif., November 17-23, 1996. Tumour Biol 19 Suppl 1:1-20
17.
Zurück zum Zitat Matsushita T, Takada W, Igarashi K et al (2014) A straightforward protocol for the preparation of high performance microarray displaying synthetic MUC1 glycopeptides. Biochim Biophys Acta 1840:1105–1116CrossRefPubMed Matsushita T, Takada W, Igarashi K et al (2014) A straightforward protocol for the preparation of high performance microarray displaying synthetic MUC1 glycopeptides. Biochim Biophys Acta 1840:1105–1116CrossRefPubMed
18.
Zurück zum Zitat Kufe D, Inghirami G, Abe M et al (1984) Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma 3:223–232CrossRefPubMed Kufe D, Inghirami G, Abe M et al (1984) Differential reactivity of a novel monoclonal antibody (DF3) with human malignant versus benign breast tumors. Hybridoma 3:223–232CrossRefPubMed
19.
Zurück zum Zitat Stahli C, Takacs B, Miggiano V et al (1985) Monoclonal antibodies against antigens on breast cancer cells. Experientia 41:1377–1381CrossRefPubMed Stahli C, Takacs B, Miggiano V et al (1985) Monoclonal antibodies against antigens on breast cancer cells. Experientia 41:1377–1381CrossRefPubMed
20.
Zurück zum Zitat Smith RA, Andrews KS, Brooks D et al (2017) Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 67:100–121CrossRefPubMed Smith RA, Andrews KS, Brooks D et al (2017) Cancer screening in the United States, 2017: a review of current American Cancer Society guidelines and current issues in cancer screening. CA Cancer J Clin 67:100–121CrossRefPubMed
21.
Zurück zum Zitat Cady B, Chung M (2005) Mammographic screening: no longer controversial. Am J Clin Oncol 28:1–4CrossRefPubMed Cady B, Chung M (2005) Mammographic screening: no longer controversial. Am J Clin Oncol 28:1–4CrossRefPubMed
22.
Zurück zum Zitat Welch HG, Prorok PC, O’Malley AJ et al (2016) Breast-cancer tumor size, overdiagnosis, and mammography screening effectiveness. N Engl J Med 375:1438–1447CrossRefPubMed Welch HG, Prorok PC, O’Malley AJ et al (2016) Breast-cancer tumor size, overdiagnosis, and mammography screening effectiveness. N Engl J Med 375:1438–1447CrossRefPubMed
23.
Zurück zum Zitat Uematsu T (2017) The need for supplemental breast cancer screening modalities: a perspective of population-based breast cancer screening programs in japan. Breast cancer 24:26–31CrossRefPubMed Uematsu T (2017) The need for supplemental breast cancer screening modalities: a perspective of population-based breast cancer screening programs in japan. Breast cancer 24:26–31CrossRefPubMed
24.
Zurück zum Zitat Ramsey SD, Henry NL, Gralow JR et al (2015) Tumor marker usage and medical care costs among older early-stage breast cancer survivors. J Clin Oncol 33:149–155CrossRefPubMed Ramsey SD, Henry NL, Gralow JR et al (2015) Tumor marker usage and medical care costs among older early-stage breast cancer survivors. J Clin Oncol 33:149–155CrossRefPubMed
25.
Zurück zum Zitat Van Poznak C, Somerfield MR, Bast RC et al (2015) Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: american society of clinical oncology clinical practice guideline. J Clin Oncol 33:2695–2704CrossRefPubMedPubMedCentral Van Poznak C, Somerfield MR, Bast RC et al (2015) Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: american society of clinical oncology clinical practice guideline. J Clin Oncol 33:2695–2704CrossRefPubMedPubMedCentral
26.
Zurück zum Zitat Duffy MJ, Evoy D, McDermott EW (2010) CA 15-3: uses and limitation as a biomarker for breast cancer. Clin Chim Acta 411:1869–1874CrossRefPubMed Duffy MJ, Evoy D, McDermott EW (2010) CA 15-3: uses and limitation as a biomarker for breast cancer. Clin Chim Acta 411:1869–1874CrossRefPubMed
27.
Zurück zum Zitat Uehara M, Kinoshita T, Hojo T et al (2008) Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer. Int J Clin Oncol 13:447–451CrossRefPubMed Uehara M, Kinoshita T, Hojo T et al (2008) Long-term prognostic study of carcinoembryonic antigen (CEA) and carbohydrate antigen 15-3 (CA 15-3) in breast cancer. Int J Clin Oncol 13:447–451CrossRefPubMed
28.
Zurück zum Zitat Sturgeon CM, Duffy MJ, Stenman UH et al (2008) National Academy of Clinical B: national academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 54:e11–79CrossRefPubMed Sturgeon CM, Duffy MJ, Stenman UH et al (2008) National Academy of Clinical B: national academy of clinical biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers. Clin Chem 54:e11–79CrossRefPubMed
29.
Zurück zum Zitat Dabrosin C (2015) An overview of pregnancy and fertility issues in breast cancer patients. Ann Med 47:673–678CrossRefPubMed Dabrosin C (2015) An overview of pregnancy and fertility issues in breast cancer patients. Ann Med 47:673–678CrossRefPubMed
30.
Zurück zum Zitat Lambertini M, Goldrat O, Clatot F et al (2017) Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art. Curr Opin Oncol 29:243–252CrossRefPubMed Lambertini M, Goldrat O, Clatot F et al (2017) Controversies about fertility and pregnancy issues in young breast cancer patients: current state of the art. Curr Opin Oncol 29:243–252CrossRefPubMed
31.
Zurück zum Zitat Lambertini M, Goldrat O, Toss A et al (2017) Fertility and pregnancy issues in brca-mutated breast cancer patients. Cancer Treat Rev 59:61–70CrossRefPubMed Lambertini M, Goldrat O, Toss A et al (2017) Fertility and pregnancy issues in brca-mutated breast cancer patients. Cancer Treat Rev 59:61–70CrossRefPubMed
Metadaten
Titel
Cross-reactivity between MUC1 antigen and MCA: false elevation of serum CA 15-3 level in pregnant and lactating women by Ma695–Ma552-based assay
verfasst von
Guangshu Liang
Xuqian Fang
Xiaoyi Lin
Xiaojing Feng
Huangying Lu
Yinglei Wan
Zhidong Gu
Publikationsdatum
02.02.2018
Verlag
Springer US
Erschienen in
Breast Cancer Research and Treatment / Ausgabe 2/2018
Print ISSN: 0167-6806
Elektronische ISSN: 1573-7217
DOI
https://doi.org/10.1007/s10549-018-4700-7

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