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


RESULTS
The expression of hepatocellular differentiation markers (Hepar, canalicular polyclonal carcinoembryonic antigen), biliary/progenitor cell markers (CK7, CK19), alpha-fetoprotein (AFP), p53 and beta-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 beta-catenin expression (P = 0.021). CK7 expression was significantly associated with elevated serum bilirubin (> 2 mg/dl) (P = 0.0005) and less nuclear beta-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.
Durnez
A
A
Department of Morphology and Molecular Pathology, KULeuven University Hospital Gasthuisberg, Belgium. anne.durnez@uz.kuleuven.ac.be
Verslype
C
C
Nevens
F
F
Fevery
J
J
Aerts
R
R
Pirenne
J
J
Lesaffre
E
E
Libbrecht
L
L
Desmet
V
V
Roskams
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D053552:Keratin-7; D007633:Keratins / Q000032:analysis*; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000601:surgery; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D011379:Prognosis; D013234:Stem Cells / Q000737:chemistry / Q000473:pathology; D044465:White People
C507497:KRT7 protein, human; D053552:Keratin-7; D007633:Keratins