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

• Published in: Histopathology Vol. 49; no. 2; pp. 138 - 151
• Main Authors: Durnez, A, Verslype, C, Nevens, F, Fevery, J, Aerts, R, Pirenne, J, Lesaffre, E, Libbrecht, L, Desmet, V, Roskams, T
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.08.2006; Blackwell
• Subjects: Adult; Aged; Aged, 80 and over; Biological and medical sciences; carcinoma; Carcinoma, Hepatocellular - metabolism; Carcinoma, Hepatocellular - pathology; Carcinoma, Hepatocellular - surgery; CK7 and CK19; European Continental Ancestry Group; Female; Gastroenterology. Liver. Pancreas. Abdomen; hepatocellular carcinoma; Humans; Immunohistochemistry; Investigative techniques, diagnostic techniques (general aspects); Keratin-7; Keratins - analysis; Liver Neoplasms - metabolism; Liver Neoplasms - pathology; Liver Neoplasms - surgery; Liver Transplantation; Liver. Biliary tract. Portal circulation. Exocrine pancreas; Male; Medical sciences; Middle Aged; Neoplasm Recurrence, Local; Pathology. Cytology. Biochemistry. Spectrometry. Miscellaneous investigative techniques; progenitor cell; Prognosis; Stem Cells - chemistry; Stem Cells - pathology; Tumors; α-fetoprotein; β-catenin; CK7 and CK19: hepatocellular carcinoma; Prognosis; Tumor associated antigen; Oncofetal antigen; Stem cell; Hepatic disease; Hepatocellular carcinoma; Cytokeratin 19; Tumoral marker; Malignant tumor; α-Fetoprotein; β-catenin; Anatomic pathology; carcinoma; β Catenin; Digestive diseases; Cytokeratin 7; Progenitor cell; Cell origin
• ISSN: 0309-0167; 1365-2559
• DOI: 10.1111/j.1365-2559.2006.02468.x

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.