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The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin
Author(s) -
Durnez A,
Verslype C,
Nevens F,
Fevery J,
Aerts R,
Pirenne J,
Lesaffre E,
Libbrecht L,
Desmet V,
Roskams T
Publication year - 2006
Publication title -
histopathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.626
H-Index - 124
eISSN - 1365-2559
pISSN - 0309-0167
DOI - 10.1111/j.1365-2559.2006.02468.x
Subject(s) - hccs , cytokeratin , hepatocellular carcinoma , pathology , medicine , keratin 7 , immunohistochemistry , transplantation , progenitor cell , stem cell , biology , genetics
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.