CA 19–9 and CE A are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis

Bjõrnsson, Einar; Kilander, Anders; Olsson, Rolf

doi:10.1111/j.1478-3231.1999.tb00083.x

Cited by 139 publications

(94 citation statements)

References 25 publications

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“…The major cause of mortality is the occurrence of cholangiocarcinoma, which is significantly increased in patients with PSC who display a 10%-15% lifetime risk of developing the disease. This risk is higher in patients with associated inflammatory bowel disease than those with PSC alone, with an estimated annual incidence of 0.5%-1% [46][47][48] . Unfortunately there remains no validated screening tool for cholangiocarcinoma and therefore tumours often present at an advanced stage and have a poor prognosis.…”

Section: Prognosismentioning

confidence: 99%

Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

Saich¹,

Chapman²

2008

WJG

117

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(AIH) is also more prevalent in patients with IBD, with up to 16% of patients with AIH also having ulcerative colitis. A small subgroup of patients have a AIH-PSC overlap syndrome and the management of these patients depends on liver histology, serum IgM levels, autoantibodies, degree of biochemical cholestasis and cholangiography as some of these patients may respond to immunosupression. INTRODUCTIONThe first association between colonic ulceration and liver disease was made in 1874 by Thomas CH, who described a young man who died of a 'much enlarged, fatty liver in the presence of ulceration of the colon' [1] . The association was confirmed by James Lister in 1899, who reported a patient with ulcerative colitis and secondary diffuse hepatitis [2] . Over the next 100 years it has become well established that there is a close relationship between inflammatory bowel disease and various hepatobiliary disorders. These disorders are listed in Table 1. PRIMARY SCLEROSING CHOLANGITISFirst described by Smith and Loe in 1965 [3] Primary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by inflammation, fibrosis and stricture formation in medium and large sized ducts in the biliary tree [4,5] . Common symptoms include itch and lethargy although many patients (up to 45%) are asymptomatic, even with advanced disease [5] . The disease is strongly associated with Inflammatory Bowel Disease and may be detected as an incidental finding of a raised serum alkaline phosphatase. www.wjgnet.comRe b e c c a S a i c h , Ro g e r C h a p m a n , AbstractPrimary sclerosing cholangitis (PSC) is a chronic progressive disorder of unknown aetiology characterised by chronic inflammation and stricture formation of the biliary tree.

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Section: Prognosismentioning

confidence: 99%

Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

Saich¹,

Chapman²

2008

WJG

117

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“…3,4 Cancer antigen (CA) 19-9 is widely used for serologic detection of biliary cancer, and has a sensitivity of 50-60% and specificity of 80%, 5 although others have found it to be a far more unreliable marker of malignancy, especially for the diagnosis of early stage cancers. 6 Similarly, detection of p53 and RAS gene mutations in bile has a sensitivity of only 33% and a specificity of 87%. 7 There is an ongoing need to identify highly sensitive and specific biomarkers for early detection of biliary tract cancer in biological samples, such as bile or serum.…”

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confidence: 99%

The V599E BRAF mutation is uncommon in biliary tract cancers

et al. 2004

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Activating point mutations of the BRAF oncogene have been identified in several solid tumors, most commonly in cutaneous melanomas and papillary carcinomas of the thyroid. A specific point mutation-V599E-accounts for the overwhelming majority of these mutational events. We explored the frequency of the V599E BRAF mutation in biliary tract cancers. In all, 62 archival biliary tract cancers, including 15 gallbladder cancers, 15 extrahepatic, and 10 intrahepatic cholangiocarcinomas from the United States, and 22 gallbladder carcinomas from Chile were analyzed for the V599E mutation of the BRAF gene using three distinct methods: direct sequencing, a primer extension method (Mutector s assay), and the highly sensitive quantitative Gap Ligase Chain Reaction. The common V599E mutation was not identified in any of the 62 biliary cancer samples using these three methods of detection. The V599E somatic mutation of the BRAF gene is absent in biliary tract cancers, at least in the two geographic populations (United States and Chile) examined. Activation of the RAS/ RAF/MAP kinase pathway in biliary tract cancers is likely to be secondary to oncogenic RAS mutations, or due to mutations of the BRAF gene at nucleotide positions not explored in the current study.

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“…Low sensitivity (33%) and high specificity (85%) were also obtained for CEA at a cut-off of 5 ng/mL by Bjo¨rnsson and colleagues. 16 Most interestingly however, there seems to be no influence of benign dominant strictures on CEA serum levels or its diagnostic performance in cancer detection.…”

Section: Discussionmentioning

confidence: 99%

A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

et al. 2016

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Background: Primary sclerosing cholangitis (PSC) patients are at increased risk of biliary tract cancer, and carcinoembryonic antigen (CEA) serum levels might be used for screening. Objective: To examine cancer screening with CEA in PSC patients and analyse how serum CEA levels are affected by genetic variants of fucosyltransferase (FUT) 2 and 3. Methods: In a retrospective cohort analysis we evaluated CEA levels in 226 PSC patients, including 19 with biliary malignancy, and investigated how FUT2 and FUT3 SNPs affected CEA levels. Receiver-operating-characteristic (ROC) analysis was performed and cut-off values were determined based on Youden's index. A control cohort contained 240 patients, including 28 with biliary malignancy. Results: Median CEA concentration was lower in cancer-free patients (1.4 ng/mL) than in cancer patients (2.0 ng/mL, P ¼ 0.014). ROC analysis revealed an area under the curve (AUC) of 0.671, the optimal cut-off was 3.2 ng/mL. The FUT2 variant rs601338 (G428A) correlated with CEA levels, and the effect was most prominent in a subgroup of patients genetically incapable of expressing CA19-9. The AUC improved if ROC analysis was performed separately for wild-type (AUC: 0.731) and homozygous mutant (AUC: 0.816) G428A. The influence of FUT2 on CEA was confirmed in the control cohort. Conclusions: CEA is interesting for biliary-malignancy screening in PSC patients, especially in patients who do not express CA19-9. This is the first study to show that the combined use of CEA measurement and FUT genotyping is clinically beneficial and that it might enhance the early detection of biliary malignancy in clinical practice. This approach could also be effective when screening for other common gastrointestinal malignancies.

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CA 19–9 and CE A are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis

Cited by 139 publications

References 25 publications

Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

Primary sclerosing cholangitis, autoimmune hepatitis and overlap syndromes in inflammatory bowel disease

The V599E BRAF mutation is uncommon in biliary tract cancers

A common genetic variant of fucosyltransferase 2 correlates with serum carcinoembryonic antigen levels and affects cancer screening in patients with primary sclerosing cholangitis

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