Lewis-negative (Lewis antigen-negative, CA 19-9 non-secretor) status

CA 19-9 is the sialylated Lewis A antigen, made by an enzyme encoded by the FUT3 (Lewis) gene; people with two non-functional FUT3 alleles, about 5 to 10 percent of the population, cannot synthesise it, and the standard account is that their CA 19-9 is undetectable whatever the tumour burden (Ballehaninna 2012). That makes CA 19-9 falsely negative in this group, one of its main limitations alongside its low positive predictive value in screening and its rise in benign biliary obstruction and pancreatitis. A prospective series of 1,482 Chinese patients with pancreatic cancer genotyped FUT3 and found 8.4 percent Lewis-negative, but only 41.9 percent of them had CA 19-9 of 2 U/mL or less and 27.4 percent had a raised level above 37 U/mL, so the marker kept diagnostic value (area under the curve 0.842 against 0.898 in all patients); Lewis-negative status itself was an independent predictor of shorter survival (hazard ratio 1.30) (Luo 2018). A further analysis of 853 patients and cell lines found Lewis-negative cancers had a higher metastatic rate, lower CA 19-9 and higher MUC16 (CA 125) expression, and Lewis-negative cell lines grew and migrated faster, describing an aggressive subgroup (Int J Oncol 2020). Practical consequences: a normal CA 19-9 in a patient with a suspicious scan should not reassure; CA 125 or CEA is followed instead in known Lewis-negative patients; and trials that use CA 19-9 for eligibility or response exclude or mis-classify this group. The parent CA 19-9 term carries the marker's other uses.