Z Gastroenterol 2012; 50 - K040
DOI: 10.1055/s-0032-1323975

FUT2 and FUT3 depending cut-off values in PSC-patients increase diagnostic accuracy of CA19–9 for detection of biliary malignancies

A Wannhoff 1, T Folseraas 2, JR Hov 2, KH Weiss 1, W Stremmel 1, TH Karlsen 2, D Gotthardt 1
  • 1University Hospital of Heidelberg, Department of Internal Medicine IV, Heidelberg, Germany
  • 2Oslo University Hospital, Rikshospitalet, Norwegian PSC Research Center, Division for Cancer, Surgery and Transplantation, Oslo, Norway

Introduction: Patients with primary sclerosing cholangitis (PSC) are at increased risk of developing biliary malignancies as cholangiocellular carcinoma (CCA) or gall bladder carcinoma (GBCA). Ultrasound and CA19–9 are the most commonly use screening parameters. FUT2- and FUT3-gene status influences CA19–9 levels.

Aims: To evaluate CA19–9 as a diagnostic marker for detecting CCA and GBCA in PSC-patients, depending on the individual's FUT2- and FUT3-gene status.

Methods: In 407 PSC-patients, among which 34 (6.9%) had CCA and 3 (0.6%) had GBCA, CA19–9 values were retrospectively analyzed. Depending on the FUT2- and FUT3-gene status and on the expected phenotypes patients were divided into three groups. Group a includes patients with homozygous FUT3-mutation regardless of FUT2-status, group c includes patients with homozygous FUT-2 mutation and group b includes all other patients. A ROC-analysis was performed and group specific cut-off values were determined.

Results: Mean CA19–9 in patients without carcinoma is 2.0 U/ml (IQR: 0.0–6.6) in group a, 17.0 U/ml (IQR: 9.0–38.8) in group b and 36.0 U/ml (IQR: 22.8–64.0) in group c. Differences are statistically significant. A cut-off of 131.5 U/ml in the whole study population results in a sensitivity of 70.3%, specificity of 93.5%, PPV of 51.1% and NPV of 97.0%. For similar PPV and NPV the cut-off value in group b is 79.0 U/ml and 272.5 U/ml in group c. ROC-analysis shows an increased AUC in groups b and c compared to the whole study population.

Conclusion: Mean CA-19–9 values and cut-off values depend on the FUT2- and FUT3-gene status in PSC-patients. Due to the FUT3-mutation, patients in group a are not able to synthesize CA19–9. Determination of FUT2 and FUT3 increases the accuracy of CA19–9 in detecting CCA and GBCA in PSC-patients and allows determination of patient specific cut-off values.