Lewis antigen and antibody testing as practical first-line approaches for detecting CA19-9 non-producers

CA19-9 is a sialylated Lewis antigen (Ag) widely used as a tumor biomarker for pancreatic and colorectal cancers. However, Lewis Ag-negative patients do not produce CA19-9, resulting in clinically relevant false-negative results. Although FUT2/FUT3 genotyping provides the most accurate determination of CA19-9 producer status, its routine clinical use is limited by cost, turnaround time (TAT), and restricted accessibility, making concurrent testing with CA19-9 impractical in most clinical settings.

This study evaluated the translational utility of Lewis Ag and antibody (Ab) testing-serologic assays routinely performed in blood banks-as practical alternatives to FUT2/FUT3 genotyping. Residual samples from 60 patients were analyzed for CA19-9 levels, Lewis Ag phenotype, Lewis Ab, and FUT2/FUT3 genotypes.

Lewis Ag and Ab testing demonstrated nearly perfect and substantial agreement with CA 19-9 status (κ = 0.85, P < 0.001; κ = 0.75, P < 0.001, respectively), comparable to FUT2/FUT3 genotyping (κ = 0.96, P < 0.001). Lewis Ag and Ab testing showed high sensitivity (90.9%), specificity (97.4%), and area under the curve (0.938, P < 0.001). In addition, Lewis Ag and Ab testing was associated with equivalent costs/test and shorter TAT compared with FUT2/FUT3 genotyping (costs/test, USD 3.50 and 6.02 vs. 4.88 + α; TAT, 16.5 and 90 vs. 200 minutes), without requiring specialized infrastructure or extensive validation procedures.

Lewis Ag and Ab testing represent a time-efficient, cost-effective, and clinically accessible alternative to FUT2/FUT3 genotyping for identifying CA19-9 non-producers, supporting their use as a first-line approach in routine clinical practice.