Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis

Sanjay Y. Bangarulingam, Einar Bjornsson, Felicity Enders, Emily G. Barr Fritcher, Gregory Gores, Kevin C. Halling, Keith Lindor

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Abstract

Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51%) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46% and 88%, and for trisomy/tetrasomy they were 25% and 67%, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88% for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).

Original languageEnglish (US)
Pages (from-to)174-180
Number of pages7
JournalHepatology
Volume51
Issue number1
DOIs
StatePublished - Jan 2010
Externally publishedYes

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Sclerosing Cholangitis
Fluorescence In Situ Hybridization
Cholangiocarcinoma
Tetrasomy
Trisomy
Cell Biology
Pathologic Constriction
Endoscopic Retrograde Cholangiopancreatography

ASJC Scopus subject areas

  • Hepatology

Cite this

Bangarulingam, S. Y., Bjornsson, E., Enders, F., Barr Fritcher, E. G., Gores, G., Halling, K. C., & Lindor, K. (2010). Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis. Hepatology, 51(1), 174-180. https://doi.org/10.1002/hep.23277

Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis. / Bangarulingam, Sanjay Y.; Bjornsson, Einar; Enders, Felicity; Barr Fritcher, Emily G.; Gores, Gregory; Halling, Kevin C.; Lindor, Keith.

In: Hepatology, Vol. 51, No. 1, 01.2010, p. 174-180.

Research output: Contribution to journalArticle

Bangarulingam, SY, Bjornsson, E, Enders, F, Barr Fritcher, EG, Gores, G, Halling, KC & Lindor, K 2010, 'Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis', Hepatology, vol. 51, no. 1, pp. 174-180. https://doi.org/10.1002/hep.23277
Bangarulingam SY, Bjornsson E, Enders F, Barr Fritcher EG, Gores G, Halling KC et al. Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis. Hepatology. 2010 Jan;51(1):174-180. https://doi.org/10.1002/hep.23277
Bangarulingam, Sanjay Y. ; Bjornsson, Einar ; Enders, Felicity ; Barr Fritcher, Emily G. ; Gores, Gregory ; Halling, Kevin C. ; Lindor, Keith. / Long-term outcomes of positive fluorescence in situ hybridization tests in primary sclerosing cholangitis. In: Hepatology. 2010 ; Vol. 51, No. 1. pp. 174-180.
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abstract = "Patients with primary sclerosing cholangitis (PSC) are at increased risk for developing cholangiocarcinoma (CCA). Fluorescence in situ hybridization (FISH) is a cytological test designed to enhance early CCA diagnosis. The long-term outcome of PSC patients with a positive FISH test (polysomy, trisomy/tetrasomy) are unclear. All PSC patients with at least one FISH test were identified and defined to have CCA if they had a positive tissue biopsy, positive cytology, or evidence of cancer in the explant after liver transplantation. A total of 235 PSC patients had at least one FISH test performed, and 56 patients had CCA on histopathology (n = 35) or cytology (n = 21). Overall, 120 of 235 (51{\%}) of PSC patients tested for FISH were positive, but only one third of these positive patients had CCA. Sensitivity and specificity for FISH polysomy were 46{\%} and 88{\%}, and for trisomy/tetrasomy they were 25{\%} and 67{\%}, respectively. Survival analysis showed that patients with FISH polysomy had an outcome similar to patients with CCA; whereas FISH trisomy/tetrasomy patients had an outcome similar to patients with negative FISH tests. The FISH polysomy patients without cancer compared with those with CCA had lower serum bilirubin, lower carbohydrate antigen 19-9 (CA 19-9), lower Mayo risk score, and lower occurrence of dominant strictures. Conclusion: In PSC patients, the presence of a dominant stricture plus FISH polysomy has a specificity of 88{\%} for CCA. Patients with FISH showing trisomy or tetrasomy have a similar outcome to patients with negative FISH. FISH testing should be used selectively in patients with other signs indicating CCA and not as a screening tool in all PSC patients undergoing endoscopic retrograde cholangiopancreatography (ERCP).",
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