The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin
Top Cited Papers
- 17 July 2006
- journal article
- Published by Wiley in Histopathology
- Vol. 49 (2), 138-151
- https://doi.org/10.1111/j.1365-2559.2006.02468.x
Abstract
Aims: Cytokeratin (CK) 7 and CK19 expression, present in hepatic progenitor cells (HPCs) and in cholangiocytes but not in normal hepatocytes, has been reported in some hepatocellular carcinomas (HCCs); however, the incidence and relevance of this expression in HCC in Caucasians is not known. Therefore, our aim was to study the occurrence and clinicopathological characteristics of HCC expressing CK7 and/or CK19 in 109 Caucasian patients. Methods and results: The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), α-fetoprotein (AFP), p53 and β-catenin in HCC was semiquantitatively assessed by immunohistochemistry. Of 109 HCCs, 78 were CK7–/CK19– (72%), 13 CK7+/CK19– (12%), seven CK7–/CK19+ (6%), 11 CK7+/CK19+ (10%). CK19 expression was significantly associated with elevated serum AFP (400 ng/ml) (P = 0.023), tumour AFP expression (P < 0.0001), presence in serum of anti-hepatitis B core (P = 0.016), less fibrosis in non-neoplastic parenchyma (P = 0.009) and less nuclear β-catenin expression (P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) (P = 0.0005) and less nuclear β-catenin expression (P = 0.003). HCC expressing CK19 had a higher rate of recurrence (P = 0.009, hazard ratio 12.5, n = 31) after liver transplantation compared with CK19– tumours. Conclusions: In our series, 28% of HCCs contained cells expressing CK7 and/or CK19. They potentially derive from HPCs. The higher recurrence rate of CK19+ HCC after transplantation suggests a worse prognosis for these HCCs compared with CK19– HCC.Keywords
This publication has 47 references indexed in Scilit:
- Clinical and molecular analysis of combined hepatocellular-cholangiocarcinomasJournal of Hepatology, 2004
- High α‐fetoprotein level correlates with high stage, early recurrence and poor prognosis of hepatocellular carcinoma: Significance of hepatitis virus infection, age, p53 and β‐catenin mutationsInternational Journal of Cancer, 2004
- Primary liver carcinoma of intermediate (hepatocyte–cholangiocyte) phenotypeJournal of Hepatology, 2004
- From Proteomic Analysis to Clinical SignificanceMolecular & Cellular Proteomics, 2004
- Clinical Characteristics and Prognosis of Hepatocellular CarcinomaJournal of Clinical Gastroenterology, 2000
- β‐Catenin Accumulation and Mutation of Exon 3 of the β‐Catenin Gene in Hepatocellular CarcinomaJapanese Journal of Cancer Research, 1999
- Primary liver tumour of intermediate (hepatocyte—bile duct cell) phenotype: a progenitor cell tumour?Liver International, 1998
- Intraobserver and interobserver variations in liver biopsy interpretation in patients with chronic hepatitis CHepatology, 1994
- Cellular origin of cancer: dedifferentiation or stem cell maturation arrest?Environmental Health Perspectives, 1993
- Keratin 14 protein in cultured nonparenchymal rat hepatic epithelial cells: Characterization of keratin 14 and keratin 19 as antigens for the commonly used mouse monoclonal antibody OV‐6Molecular Carcinogenesis, 1993