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

(2006) HISTOPATHOLOGY. 49(2). p.138-151
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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), 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.
Keywords
beta-catenin, alpha-fetoprotein, carcinoma, CK7 and CK19, hepatocellular carcinoma, progenitor cell, HUMAN-LIVER, EPITHELIAL-CELLS, BETA-CATENIN, DIFFERENTIAL-DIAGNOSIS, MONOCLONAL-ANTIBODIES, CLINICAL-SIGNIFICANCE, VIRUS-INFECTION, C-MYC, CHOLANGIOCARCINOMA, HEPATOCYTE

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MLA
Durnez, A, C Verslype, F Nevens, et al. “The Clinicopathological and Prognostic Relevance of Cytokeratin 7 and 19 Expression in Hepatocellular Carcinoma: a Possible Progenitor Cell Origin.” HISTOPATHOLOGY 49.2 (2006): 138–151. Print.
APA
Durnez, A., Verslype, C., Nevens, F., Fevery, J., Aerts, R., Pirenne, J., Lesaffre, E., et al. (2006). The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma: a possible progenitor cell origin. HISTOPATHOLOGY, 49(2), 138–151.
Chicago author-date
Durnez, A, C Verslype, F Nevens, J Fevery, R Aerts, J Pirenne, E Lesaffre, Louis Libbrecht, V Desmet, and T Roskams. 2006. “The Clinicopathological and Prognostic Relevance of Cytokeratin 7 and 19 Expression in Hepatocellular Carcinoma: a Possible Progenitor Cell Origin.” Histopathology 49 (2): 138–151.
Chicago author-date (all authors)
Durnez, A, C Verslype, F Nevens, J Fevery, R Aerts, J Pirenne, E Lesaffre, Louis Libbrecht, V Desmet, and T Roskams. 2006. “The Clinicopathological and Prognostic Relevance of Cytokeratin 7 and 19 Expression in Hepatocellular Carcinoma: a Possible Progenitor Cell Origin.” Histopathology 49 (2): 138–151.
Vancouver
1.
Durnez A, Verslype C, Nevens F, Fevery J, Aerts R, Pirenne J, et al. The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma: a possible progenitor cell origin. HISTOPATHOLOGY. 2006;49(2):138–51.
IEEE
[1]
A. Durnez et al., “The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma: a possible progenitor cell origin,” HISTOPATHOLOGY, vol. 49, no. 2, pp. 138–151, 2006.
@article{3183524,
  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), 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.},
  author       = {Durnez, A and Verslype, C and Nevens, F and Fevery, J and Aerts, R and Pirenne, J and Lesaffre, E and Libbrecht, Louis and Desmet, V and Roskams, T},
  issn         = {0309-0167},
  journal      = {HISTOPATHOLOGY},
  keywords     = {beta-catenin,alpha-fetoprotein,carcinoma,CK7 and CK19,hepatocellular carcinoma,progenitor cell,HUMAN-LIVER,EPITHELIAL-CELLS,BETA-CATENIN,DIFFERENTIAL-DIAGNOSIS,MONOCLONAL-ANTIBODIES,CLINICAL-SIGNIFICANCE,VIRUS-INFECTION,C-MYC,CHOLANGIOCARCINOMA,HEPATOCYTE},
  language     = {eng},
  number       = {2},
  pages        = {138--151},
  title        = {The clinicopathological and prognostic relevance of cytokeratin 7 and 19 expression in hepatocellular carcinoma: a possible progenitor cell origin},
  url          = {http://dx.doi.org/10.1111/j.1365-2559.2006.02468.x},
  volume       = {49},
  year         = {2006},
}

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