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

Source: https://onco.cc/terms/lewis-negative/  
OnCo record `lewis-negative` (Term). Data CC BY-NC 4.0, attribute "Data from OnCo (onco.cc)"; commercial use needs a licence.

## TL;DR

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.

## Fields

- Kind: Term
- Last checked: 2026-09-24
- Also known as: Lewis antigen-negative; Lewis negative phenotype; CA 19-9 non-secretor; FUT3 null; Lewis blood group negative; Le(a-b-)
- Tags: gi; pancreatic

## Sources

- Wikipedia: https://en.wikipedia.org/wiki/CA19-9
- Ballehaninna and Chamberlain, J Gastrointest Oncol 2012: clinical utility of serum CA 19-9 in pancreatic adenocarcinoma: https://doi.org/10.3978/j.issn.2078-6891.2011.021
- Luo, Pancreatology 2018: CA19-9 in Lewis-negative patients with pancreatic cancer (1,482 patients): https://doi.org/10.1016/j.pan.2018.08.003
- Int J Oncol 2020: Lewis antigen-negative pancreatic cancer, an aggressive subgroup (853 patients): https://doi.org/10.3892/ijo.2020.4989

## Connected records

- cancers: [Biliary tract cancer (cholangiocarcinoma)](https://onco.cc/cancers/cholangiocarcinoma/), [Metastatic pancreatic ductal adenocarcinoma](https://onco.cc/cancers/metastatic-pdac/), [Pancreatic ductal adenocarcinoma](https://onco.cc/cancers/pancreatic/)
- technologies: [Liquid biopsy (ctDNA)](https://onco.cc/technologies/liquid-biopsy/)
- terms: [CA 19-9](https://onco.cc/terms/ca19-9/), [Positive predictive value (PPV)](https://onco.cc/terms/ppv/)
- key papers: [Relationship of carbohydrate antigen 19-9 and Lewis antigens in pancreatic cancer](https://onco.cc/key-papers/paper-tempero-ca19-9-lewis-antigens-cancer-res-1987/)

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