{"entity":{"id":"lewis-negative","kind":"term","name":"Lewis-negative (Lewis antigen-negative, CA 19-9 non-secretor) status","aka":["Lewis antigen-negative","Lewis negative phenotype","CA 19-9 non-secretor","FUT3 null","Lewis blood group negative","Le(a-b-)"],"tldr":"About one person in ten to twenty cannot make the sugar that the CA 19-9 blood test measures, because they lack a working copy of the Lewis blood-group gene. In these Lewis-negative people the test stays low however large the cancer, so a normal CA 19-9 does not rule pancreatic cancer out, and their cancers appear to behave more aggressively.","summary":"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.","asOf":"2026-09-24","wikipedia":"https://en.wikipedia.org/wiki/CA19-9","links":[{"label":"Ballehaninna and Chamberlain, J Gastrointest Oncol 2012: clinical utility of serum CA 19-9 in pancreatic adenocarcinoma","url":"https://doi.org/10.3978/j.issn.2078-6891.2011.021"},{"label":"Luo, Pancreatology 2018: CA19-9 in Lewis-negative patients with pancreatic cancer (1,482 patients)","url":"https://doi.org/10.1016/j.pan.2018.08.003"},{"label":"Int J Oncol 2020: Lewis antigen-negative pancreatic cancer, an aggressive subgroup (853 patients)","url":"https://doi.org/10.3892/ijo.2020.4989"}],"tags":["gi","pancreatic"],"related":[],"cancers":["pancreatic","metastatic-pdac","cholangiocarcinoma"],"sections":[],"technologies":["liquid-biopsy"],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":["ca19-9","ppv"],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":[],"dependsOn":[],"notes":[],"category":"Biomarkers"},"route":"/terms/lewis-negative/","neighbours":{"cancer":[{"id":"cholangiocarcinoma","kind":"cancer","name":"Biliary tract cancer (cholangiocarcinoma)","route":"/cancers/cholangiocarcinoma/"},{"id":"metastatic-pdac","kind":"cancer","name":"Metastatic pancreatic ductal adenocarcinoma","route":"/cancers/metastatic-pdac/"},{"id":"pancreatic","kind":"cancer","name":"Pancreatic ductal adenocarcinoma","route":"/cancers/pancreatic/"}],"technology":[{"id":"liquid-biopsy","kind":"technology","name":"Liquid biopsy (ctDNA)","route":"/technologies/liquid-biopsy/"}],"term":[{"id":"ca19-9","kind":"term","name":"CA 19-9","route":"/terms/ca19-9/"},{"id":"ppv","kind":"term","name":"Positive predictive value (PPV)","route":"/terms/ppv/"}],"paper":[{"id":"paper-tempero-ca19-9-lewis-antigens-cancer-res-1987","kind":"paper","name":"Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer","route":"/key-papers/paper-tempero-ca19-9-lewis-antigens-cancer-res-1987/"}]}}