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Bile detection of squamous cell carcinoma antigen (SCCA) in extrahepatic cholangiocarcinoma

  • E. Gringeri
    Correspondence
    Corresponding author at: Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy.
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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  • A. Biasiolo
    Affiliations
    European Reference Network - ERN RARE-LIVER, Germany

    Department of Medicine, Medical Clinic 5, University of Padua, Via Giustiniani, 2, Padova 35128, Italy
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  • M. Di Giunta
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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  • C. Mescoli
    Affiliations
    Pathology Unit, Padua University Hospital, Via Giustiniani, 2, Padova 35128, Italy
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  • V. Guzzardo
    Affiliations
    Pathology Unit, Padua University Hospital, Via Giustiniani, 2, Padova 35128, Italy
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  • A. Sartori
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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  • G. Cirillo
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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  • E. Nieddu
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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  • F.E. D'Amico
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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  • P. Pontisso
    Affiliations
    European Reference Network - ERN RARE-LIVER, Germany

    Department of Medicine, Medical Clinic 5, University of Padua, Via Giustiniani, 2, Padova 35128, Italy
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  • U. Cillo
    Affiliations
    Department of Surgery, Oncology and Gastroenterology, HPB Surgery and Liver Transplantation Unit, Padova University Hospital, Via Giustiniani, 2, Padova 35128, Italy

    European Reference Network - ERN RARE-LIVER, Germany
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Published:November 08, 2022DOI:https://doi.org/10.1016/j.dld.2022.10.010

      Abstract

      Background

      Cholangiocarcinoma (CCA) is a rare biliary tract tumor with poor prognosis that often is challenging to diagnose and the majority of patients present with advanced stage. Squamous cell carcinoma antigen 1 (SCCA1) overexpression has been found in different tumors associated with poor prognosis and chemoresistance.

      Aims

      To assess the presence and possible prognostic role of SCCA1/2 isoforms in bile and serum of patients with CCA.

      Methods

      Forty seven surgical patients (36 with CCA and 11 with benign diseases) were prospectively included in the study. Serum and bile specimens were collected at the time of surgery and free and IgM-complexed SCCA was quantified by ELISA (Xeptagen, srl).

      Results

      Free or IgM linked SCCA was rarely found in serum, while SCCA was detectable in bile samples of patients with CCA, especially in those with extrahepatic form (43% vs 17%, p = 0.008), but not in controls. Despite similar tumor stage, these positive patients presented a trend toward a higher percentage of portal invasion (27% vs 15%) and of tumor recurrence than negative cases (62% vs 40%), although the difference was not statistically significant.

      Conclusion

      These preliminary results indicate that bile testing for SCCA is a specific marker of extrahepatic CCA, with potential prognostic value.

      Keywords

      Abbreviations:

      CCA (Cholangiocarcinoma), i-CCA (intrahepatic cholangiocarcinoma), e-CCA (extrahepatic cholangiocarcinoma), d-CCA (distal cholangiocarcinoma), p-CCA (perihilar cholangiocarcinoma)
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      References

        • Rizvi S.
        • Gores G.J.
        Pathogenesis, diagnosis and management of cholangiocarcinoma.
        Gastroenterology. 2013; 145: 1215-1229
        • Banales J.M.
        • Marin J.J.G.
        • Lamarca A.
        • et al.
        Cholangiocarcinoma 2020: the next horizon in mechanisms and management.
        Nat Rev Gastroenterol Hepatol. 2020; 17: 577-588
        • Corentin L.
        • Panagiotis P.
        • Cédric C.
        Molecular classification of cholangiocarcinoma.
        Curr Opin Gastroenterol. 2020; 36: 57-62
        • Chung B.K.
        • Karlsen T.H.
        • Folseraas T.
        • et al.
        Cholangiocytes in the pathogenesis of primary sclerosing cholangitis and development of cholangiocarcinoma.
        Biochim Biophys Acta Mol Basis Dis. 2018; 1864: 1390-1400
        • Patel A.H.
        • Harnois D.M.
        • Klee G.G.
        The utility of CA 19-9 in the diagnoses of cholangiocarcinoma in patients without primary sclerosing cholangitis.
        Am J Gastroenterol. 2000; 95: 204-207
        • Loosen S.H.
        • Roderburg C.
        • Kauertz K.L.
        • et al.
        CEA but not CA19-9 is an independent prognostic factor in patients undergoing resection of cholangiocarcinoma.
        Sci Rep. 2017; 7: 16975
        • Björnsson E.
        • Kilander A.
        • Olsson R.
        CA 19-9 and CEA are unreliable markers for cholangiocarcinoma in patients with primary sclerosing cholangitis.
        Liver. 1999; 19: 501-508
        • Banales J.M.
        • Iñarrairaegui M.
        • Arbelaiz A.
        • et al.
        Serum metabolites as diagnostic biomarkers for cholangiocarcinoma, hepatocellular Carcinoma, and primary sclerosing cholangitis.
        Hepatology. 2019; 70: 547-562
        • Macias R.I.R.
        • Kornek M.
        • Rodrigues P.M
        • et al.
        Diagnostic and prognostic biomarkers in cholangiocarcinoma.
        Liver Int. 2019; 39: 108-122
        • Boilève A.
        • Hilmi M.
        • Delaye M.
        • et al.
        Biomarkers in hepatobiliary cancers: what is useful in clinical practice?.
        Cancers. 2021; 13 (Basel): 2708
        • Brunt E.
        • Aishima S.
        • Clavien P.A.
        • et al.
        HCC-CCA: consensus terminology for primary liver carcinomas with both hepatocytic and cholangiocytic differentation.
        Hepatology. 2018; 68: 113-126
        • Villano G.
        • Turato C.
        • Quarta S.
        • et al.
        Hepatic progenitor cells express SerpinB3.
        BMC Cell Biol. 2014; 15: 5
        • Guido M.
        • Roskams T.
        • Pontisso P.
        • et al.
        Squamous cell carcinoma antigen in human liver carcinogenesis.
        J Clin Pathol. 2008; 61: 445-447
        • Turato C.
        • Buendia M.A.
        • Fabre M.
        • et al.
        Over-expression of SERPINB3 in hepatoblastoma: a possible insight into the genesis of this tumour?.
        Eur J Cancer. 2012; 48: 1219-1226
        • Turato C.
        • Vitale A.
        • Fasolato S.
        • et al.
        SERPINB3 is associated with TGF-β1 and cytoplasmic β-catenin expression in hepatocellular carcinomas with poor prognosis.
        Br J Cancer. 2014; 110: 2708-2715
        • Turato C.
        • Scarpa M.
        • Kotsafti A.
        • et al.
        Squamous cell carcinoma antigen 1 is associated to poor prognosis in esophageal cancer through immune surveillance impairment and reduced chemosensitivity.
        Cancer Sci. 2019; 110: 1552-1563
        • Beneduce L.
        • Castaldi F.
        • Marino M.
        • et al.
        Squamous cell carcinoma antigen immunoglobulin M complexes as novel biomarkers for hepatocellular carcinoma.
        Cancer. 2005; 103: 2558-2565
        • Pozzan C.
        • Cardin R.
        • Piciocchi M.
        • et al.
        Diagnostic and prognostic role of SCCA-IgM serum levels in hepatocellular carcinoma (HCC).
        J Gastroenterol Hepatol. 2014; 29: 1637-1644
        • Biasiolo A.
        • Tono N.
        • Ruvoletto M.
        • et al.
        IgM-linked SerpinB3 and SerpinB4 in sera of patients with chronic liver disease.
        PLoS One. 2012; 7: e40658
        • Cagnin M.
        • Biasiolo A.
        • Martini A.
        • et al.
        Serum squamous cell carcinoma antigen-immunoglobulin M complex levels predict survival in patients with cirrhosis.
        Sci Rep. 2019; 9: 20126
        • Correnti M.
        • Cappon A.
        • Pastore M.
        • et al.
        The protease -inhibitor SerpinB3 as a critical modulator of the stem-like subset in human cholangiocarcinoma.
        Liver Int. 2021; (Online ahead of print)https://doi.org/10.1111/liv.15049
        • Vidalino L.
        • Doria A.
        • Quarta S.
        • et al.
        SerpinB3, apoptosis and autoimmunity.
        Autoimm Rev. 2009; 9: 108-112
        • Ciscato F.
        • Sciacovelli M.
        • Villano G.
        • et al.
        SERPINB3 protects from oxidative damage by chemotherapeutics through inhibition of mitochondrial respiratory complex I.
        Oncotarget. 2014; 5: 2418-2427
        • Quarta S.
        • Vidalino L.
        • Turato C.
        • et al.
        SERPINB3 induces epithelial mesenchymal transition.
        J Path. 2010; 221: 343-356
        • Turato C.
        • Calabrese F.
        • Biasiolo A.
        • et al.
        SERPINB3 modulates TGF-beta expression in chronic liver disease.
        Lab Invest. 2010; 90: 1016-1023
        • Novo E.
        • Villano G.
        • Turato C.
        • et al.
        SerpinB3 promotes Pro-fibrogenic responses in activated hepatic stellate cells.
        Sci Rep. 2017; 7: 3420
        • Turato C.
        • Cannito S.
        • Simonato D.
        • et al.
        SerpinB3 and yap interplay increases Myc oncogenic activity.
        Sci Rep. 2015; 5: 17701
        • Terrin L.
        • Agostini M.
        • Ruvoletto M.
        • et al.
        SerpinB3 upregulates the Cyclooxygenase-2 /β-Catenin positive loop in colorectal cancer.
        Oncotarget. 2017; 8: 15732-15743
        • Hau H.M.
        • Meyer F.
        • Jahn N.
        • et al.
        Prognostic relevance of the eighth edition of TNM classification for resected perihilar cholangiocarcinoma.
        J Clin Med. 2020; 9: 3152
        • Tella S.H.
        • Kommalapati A.
        • Yadav S.
        • et al.
        Novel staging system using carbohydrate antigen (CA) 19-9 in extra-hepatic cholangiocarcinoma and its implications on overall survival.
        Eur J Surg Oncol. 2020; 46: 789-795