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J Hepatol. 2013 Dec;59(6):1278-84. doi: 10.1016/j.jhep.2013.08.005. Epub 2013 Aug 16.

FUT2 and FUT3 genotype determines CA19-9 cut-off values for detection of cholangiocarcinoma in patients with primary sclerosing cholangitis.

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1
Department of Internal Medicine IV, University Hospital of Heidelberg, Heidelberg, Germany.

Abstract

BACKGROUND & AIMS:

Allelic variants of fucosyltransferases 2 and 3 (FUT2/3) influence serum levels of CA19-9, a screening parameter commonly used for detection of biliary malignancy in PSC. We aimed at improving diagnostic accuracy of CA19-9 by determining the impact of FUT2/3 genotypes.

METHODS:

CA19-9 levels were measured in 433 PSC patients, 41 of whom had biliary malignancy. Genotypes for FUT3 and FUT2 were used to assign patients to one of three groups: A, no FUT3 activity regardless of FUT2 activity; B, both FUT2 and FUT3 activity and C, no FUT2 activity without loss of FUT3 activity. Group-specific cut-off values were determined by Youden's index.

RESULTS:

The median CA19-9 values of cancer-free patients were significantly different (p<0.001) in Groups A (2.0U/ml), B (17.0U/ml), and C (37.0U/ml). Biliary malignancy patients in Groups B and C had significantly higher CA19-9 values than cancer-free patients (p<0.001). The optimal cut-off, as determined by ROC analysis, for all patients was 88.5U/ml. Optimal cut-off values in Groups A, B, and C were 4.0U/ml, 74.5U/ml, and 106.8U/ml, respectively. Use of these values improved sensitivity of CA19-9 in Groups B and C. Further, use of group-dependent cut-off values with 90% sensitivity resulted in a 42.9% reduction of false positive results.

CONCLUSIONS:

Use of FUT2/3 genotype-dependent cut-off values for CA19-9 improved sensitivity and reduced the number of false positive results.

KEYWORDS:

AASLD; AUC; American Association for the Study of Liver Diseases; CA19-9; CCA; Cholangiocarcinoma; EASL; European Association for the Study of the Liver; FUT2; FUT3; Fucosyltransferase 2; Fucosyltransferase 3; GBCA; Gallbladder carcinoma; HD; Heidelberg; IBD; IQR; LT; MELD; Model of End-Stage Liver Disease; NPV; O; Oslo; PPV; PSC; Primary sclerosing cholangitis; ROC; SNP; WGA; area under the curve; carbohydrate antigen 19-9; cholangiocarcinoma; fucosyltransferase 2; fucosyltransferase 3; gallbladder carcinoma; inflammatory bowel disease; inter-quartile range; liver transplantation; negative predictive value; positive predictive value; primary sclerosing cholangitis; receiver operating characteristic; single-nucleotide polymorphism; whole-genome amplified

PMID:
23958938
DOI:
10.1016/j.jhep.2013.08.005
[Indexed for MEDLINE]
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