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

• Published in: Breast cancer research and treatment Vol. 169; no. 2; pp. 341 - 347
• Main Authors: Liang, Guangshu, Fang, Xuqian, Lin, Xiaoyi, Feng, Xiaojing, Lu, Huangying, Wan, Yinglei, Gu, Zhidong
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.06.2018; Springer; Springer Nature B.V
• Subjects: Adult; Analysis; Antigen-antibody reactions; Antigens; Antigens, Tumor-Associated, Carbohydrate - blood; Architects; Breast cancer; Breast Neoplasms - blood; Breast Neoplasms - pathology; Cancer research; Clinical Trial; Cross-reactivity; Female; Healthy Volunteers; Humans; Immunoprecipitation; Medicine; Medicine & Public Health; Monoclonal antibodies; MUC-1 antigen; Mucin; Mucin-1 - blood; Mucins; Neoplasms - blood; Neoplasms - pathology; Oncology; Postpartum; Pregnancy; Pregnancy Complications, Neoplastic - blood; Pregnancy Complications, Neoplastic - pathology; Pregnant women; Western blotting; Womens health; Specificity and affinity; Serum CA 15-3; Mucin-like carcinoma-associated antigen; Cross-reactivity; MUC1 monoclonal antibody
• ISSN: 0167-6806; 1573-7217; 1573-7217
• DOI: 10.1007/s10549-018-4700-7

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.