New Immunoassays for MUC1 in Breast Cancer

Abstract

Eleven experimental immunofluorometric assays (IFMAs) were made using antibodies previously tested for epitope specificities. These assays were compared with six commercially available immunoassays. The clinical performance of these experimental assays was evaluated by analysing sera from 138 breast cancer patients and 105 female blood donors. The clinical performance of these assays was evaluated at a set specificity of 0.94. The highest overall sensitivity (0.56) was observed in the experimental assay with the antibody BC2 as solid phase and GP1.4 as the tracer antibody. This combination also showed the highest sensitivity in stage I/II breast cancer. The Truquant assay (Biomira) had an overall sensitivity of 0.51, and the highest sensitivity in stages III and IV at 0.65 and 0.94, respectively. The remaining commercial assays, with sensitivity ranging from 0.67 to 0.79, were below the top five experimental assays that showed sensitivity values between 0.79 and 0.85. The findings from our current study suggest that further development in MUC1 immunoassays could improve the detection of relapse in breast cancer patients.

MUC1 Serum Assays in Breast Cancer: Tumor Specificities and Reference Levels

“…This result is partly due to the higher MUC1 levels in patients with benign diseases of the breast. A previous study from our group reported a high sensitivity, (0.41), for the BC2/GP1.4 assay for stage I/II breast cancer [19]. This high sensitivity could not be confirmed by this second, larger study.…”

“…We later established a robust and automated immunofluorometric assay [18] for further evaluation of potential tumor-specific pairs of mAbs for assays. In the latest report, eleven experimental immunoassays were evaluated together with six commercially available immunoassays [19]. An assay combination of mAbs BC2 and GP1.4 was found to have the highest sensitivity for early-stage breast cancer among the tested assays.…”

Tumor Marker Workshops

“…The epitope masking effects of carbohydrate groups were subsequently followed up by one of the workshop participants [14] who also identified and characterized corresponding carbohydrate-specific antibodies from human serum [15]. Advances continue to be made in MUC1 serum assays [16][17][18][19] and with serial determinations, of this and other markers such as CEA, represents a valuable asset in breast cancer theranostics.…”

MUC1: Antibodies and Immunoassays

“…Recently this group established a robust and automated immunofluorometric assay [12] that will facilitate the study of large numbers of antibody pairs with a view to creating better assays. In a follow-up report, this group [13] has used this method together with the most promising antibody combinations from the workshop [11] and compared these with a representative selection of currently available commercial assays. The authors have demonstrated several antibody combinations that have a greater sensitivity than the majority of commercial assays tested.…”

“…That such an apparently minor difference in epitope structure should have such a significant difference in assay sensitivity is intriguing, but highlights the need to determine antibody combinations empirically. Furthermore, differences between the b-12/MF06 experimental assay and the MCA (Roche) commercial assay, which use antibodies with identical epitopes (DTRPAP), clearly show that it is impossible to predict the diagnostic performance of MUC1 antibodies [13].…”