Serum and tissue markers in hepatocellular carcinoma and cholangiocarcinoma: clinical and prognostic implications

Massimiliano Berretta _, Carla Cavaliere, Lara Alessandrini, Brigida Stanzione, Gaetano Facchini, Luca Balestreri, Tiziana Perin and Vincenzo Canzonieri

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Oncotarget. 2017; 8:14192-14220. https://doi.org/10.18632/oncotarget.13929

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Massimiliano Berretta1, Carla Cavaliere2, Lara Alessandrini3,*, Brigida Stanzione1,*, Gaetano Facchini4, Luca Balestreri5, Tiziana Perin3 and Vincenzo Canzonieri3

1 Department of Medical Oncology, National Cancer Institute, Aviano (PN), Italy

2 Department of Onco-Ematology Medical Oncology, S.G. Moscati Hospital of Taranto Taranto, Italy

3 Division of Pathology, National Cancer Institute, Aviano (PN), Italy

4 Department of Medical Oncology, National Cancer Institute, “G. Pascale” Foundation, Naples, Italy

5 Department of Radiology, National Cancer Institute, Aviano (PN), Italy

* These authors have contributed equally to this work

Correspondence to:

Massimiliano Berretta, email:

Keywords: hepatocellular carcinoma, cholangiocarcinoma, serum markers, tissue markers, prognosis, metastasis

Received: September 16, 2016 Accepted: October 28, 2016 Published: December 14, 2016


HCC represents the sixth most common cancer worldwide and the second leading cause of cancer-related death. Despite the high incidence, treatment options for advanced HCC remain limited and unsuccessful, resulting in a poor prognosis. Despite the major advances achieved in the diagnostic management of HCC, only one third of the newly diagnosed patients are presently eligible for curative treatments. Advances in technology and an increased understanding of HCC biology have led to the discovery of novel biomarkers. Improving our knowledge about serum and tissutal markers could ultimately lead to an early diagnosis and better and early treatment strategies for this deadly disease. Serum biomarkers are striking potential tools for surveillance and early diagnosis of HCC thanks to the non-invasive, objective, and reproducible assessments they potentially enable. To date, many biomarkers have been proposed in the diagnosis of HCC. Cholangiocarcinoma (CCA) is an aggressive malignancy, characterized by early lymph node involvement and distant metastasis, with 5-year survival rates of 5%-10%. The identification of new biomarkers with diagnostic, prognostic or predictive value is especially important as resection (by surgery or combined with a liver transplant) has shown promising results and novel therapies are emerging. However, the relatively low incidence of CCA, high frequency of co-existing cholestasis or cholangitis (primary sclerosing cholangitis –PSC- above all), and difficulties with obtaining adequate samples, despite advances in sampling techniques and in endoscopic visualization of the bile ducts, have complicated the search for accurate biomarkers. In this review, we attempt to analyze the existing literature on this argument.

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