2016, Number 3
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Ann Hepatol 2016; 15 (3)
Cytokeratin19 positive hepatocellular carcinoma is associated with increased peritumoral ductular reaction
Cai X, Feng L, Liu H, Xu M, Qu Y, Wan X, Gao C, Lu L
Language: English
References: 19
Page: 386-393
PDF size: 413.12 Kb.
ABSTRACT
Background and aims. Cytokeratin19 positive (CK19+) hepatocellular carcinoma (HCC) is thought to derive from liver progenitor
cells (LPC). However, whether peritumoralductular reaction (DR) differs between CK19+ and CK19 negative (CK19-) HCC patients
remains unclear.
Material and methods. One hundred and twenty HBV-related HCC patients were enrolled in this study. Clinicopathological
variables were collected, and immunohistochemistry staining for CK19, proliferating cell nuclear antigen (PCNA), interleukin-
6 (IL-6) and β-catenin were performed in tumor and peritumor liver tissues.
Results. CK19+ HCC patients had higher grade
of peritumoral DR and proportion of proliferative DR than the CK19- group. The mean number or the proportion of cytoplasmic β-catenin+
DR was higher in the CK19+ group than in the CK19- group. Furthermore, there were more patients with nuclear β-catenin+
peritumoral DR in the CK19+ group as compared to the CK19- group.
Conclusion. Peritumoral DR was more abundant and proliferative
in CK19+ HCC patients, with higher level of nuclear translocation of β-catenin. However, it is unclear whether peritumoral DR
is the cause or result of poor prognosis in these patients.
REFERENCES
Lee JS, Heo J, Libbrecht L, Chu IS, Kaposi-Novak P, Calvisi DF, Mikaelyan A, et al. A novel prognostic subtype of human hepatocellular carcinoma derived from hepatic progenitor cells. Nat Med 2006; 12: 410-6.
Govaere O, Komuta M, Berkers J, Spee B, Janssen C, de Luca F, Katoonizadeh A, et al. Keratin 19: a key role player in the invasion of human hepatocellular carcinomas. Gut 2014; 63: 674-85.
Woo HG, Lee JH, Yoon JH, Kim CY, Lee HS, Jang JJ, Yi NJ, et al. Identification of a cholangiocarcinoma-like gene expression trait in hepatocellular carcinoma.Cancer Res 2010;70: 3034-41.
Andersen JB, Loi R, Perra A, Factor VM, Ledda-Columbano GM, Columbano A, Thorgeirsson SS. Progenitor-derived hepatocellular carcinoma model in the rat. Hepatology 2010; 51: 1401-9.
Mokkapati S, Niopek K, Huang L, Cunniff KJ, Ruteshouser EC, deCaestecker M, Finegold MJ, et al. b-catenin activation in a novel liver progenitor cell type is sufficient to cause hepatocellular carcinoma and hepatoblastoma. Cancer Res 2014; 74: 4515-25.
Tang Y, Kitisin K, Jogunoori W, Li C, Deng CX, Mueller SC, Ressom HW, et al. Progenitor/stem cells give rise to liver cancer due to aberrant TGF-beta and IL-6 signaling. Proc Natl Acad Sci USA 2008; 105: 2445-50.
Desmet VJ. Ductal plates in hepatic ductular reactions.Hypothesis and implications. I. Types of ductular reaction reconsidered. Virchows Arch 2011; 458: 251-9.
Cai X, Zhai J, Kaplan DE, Zhang Y, Zhou L, Chen X, Qian G, et al. Background progenitor activation is associated with recurrence after hepatectomy of combined hepatocellular-cholangiocarcinoma. Hepatology 2012; 56: 1804-16.
Xu M, Xie F, Qian G, Jing Y, Zhang S, Gao L, Zheng T, et al. Peritumoralductular reaction: a poor postoperative prognostic factor for hepatocellular carcinoma. BMC Cancer 2014; 14: 65.
Sobin LH, Gospodarowicz MK, Wittekind C, International Union against Cancer. TNM classification of malignant tumours, 7th ed.Chichester, UK, Hoboken, NJ: Wiley-Blackwell; 2010, p. 110-14.
Scheuer PJ. Classification of chronic viral hepatitis: a need for reassessment. J Hepatol 1991; 13: 372-4.
Clouston AD, Powell EE, Walsh MJ, Richardson MM, Demetris AJ, Jonsson JR. Fibrosis correlates with a ductular reaction in hepatitis C: roles of impaired replication, progenitor cells and steatosis. Hepatology 2005; 41: 809-18.
Gadd VL, Skoien R, Powell EE, Fagan KJ, Winterford C, Horsfall L, Irvine K, et al.The portal inflammatory infiltrate and ductular reaction in human nonalcoholic fatty liver disease. Hepatology 2014; 59: 1393-405.
Wood MJ, Gadd VL, Powell LW, Ramm GA, Clouston AD. Ductular reaction in hereditary hemochromatosis: the link between hepatocyte senescence and fibrosis progression. Hepatology 2014; 59: 848-57.
Ye F, Jing YY, Guo SW, Yu GF, Fan QM, Qu FF, Gao L, et al.Proliferative ductular reactions correlate with hepatic progenitor cell and predict recurrence in HCC patients after curative resection. Cell Biosci 2014; 4: 50.
Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, Lesaffre E, et al. The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin. Histopathology 2006; 49: 138-51.
He G1, Dhar D, Nakagawa H, Font-Burgada J, Ogata H, Jiang Y, Shalapour S, et al.Identification of liver cancer progenitors whose malignant progression depends on autocrine IL-6 signaling. Cell 2013; 155: 384-96.
Pez F, Lopez A, Kim M, Wands JR, Caron de Fromentel C, Merle P. Wnt signaling and hepatocarcinogenesis: molecular targets for the development of innovative anticancer drugs. J Hepatol 2013; 59: 1107-17.
Zulehner G, Mikula M, Schneller D, van Zijl F, Huber H, Sieghart W, Grasl-Kraupp B, et al. Nuclear beta-catenin induces an early liver progenitor phenotype in hepatocellular carcinoma and promotes tumor recurrence. Am J Pathol 2010; 176: 472-81.