The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma. A possible progenitor cell origin

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.