title: Cancer stem cells in hepatocellular carcinoma--an immunohistochemical study with histopathological association.
abstract: OBJECTIVE
  Cancer stem cells (CSCs) may be responsible for tumour recurrence and resistance to chemotherapy in hepatocellular carcinoma (HCC). This study was carried out to evaluate the association between histological parameters and liver CSCs (LCSC) in HCC, and to compare distribution of liver CSCs in HCC associated with and without hepatitis B virus (HBV) infection.
  
  
  METHODS
  Seventy nine tumours (49 surgical resections from 46 patients, and 30 from autopsy) were reviewed. Immunohistochemical staining for the LCSC marker EpCAM (epithelial cell adhesion molecule), liver progenitor cell (LPC) markers CK19 (cytokeratin 19) and neural cell adhesion molecule (NCAM) were performed and were associated with histological features of tumour behaviour.
  
  
  RESULTS
  Thirty three tumours (41.8%) showed positive staining for EpCAM. CK19 and NCAM expression were seen in 26 (32.9%) and four (5.1%) tumours, respectively. The expression of EpCAM and CK19 was significantly associated with each other ( P<0.001). EpCAM expression was significantly associated with clinical and histological features indicating aggressive tumour behaviour, including younger age of onset, higher serum alpha foetoprotein (AFP) levels, tumour cell dedifferentiation, increased mitotic activity, and vascular invasiveness. There was no significant difference in expression of EpCAM, CK19 and NCAM between HBV positive and negative HCC.
  
  
  CONCLUSIONS
  The LCSC marker EpCAM was expressed in less than half of HCC, was independent of HBV aetiology, and was strongly associated with clinical and histological features of aggressive tumour behaviour. Positive staining for CK19 suggests a possible LPC origin of the EpCAM positive HCCs.
authors.forename: Smita Mary
authors.initials: SM
authors.lastname: Matthai
authors.affiliation: Department of Pathology, Christian Medical College, Vellore, India.
authors.forename: Banumathi
authors.initials: B
authors.lastname: Ramakrishna
mesh_terms: D000328:Adult; D000368:Aged; D001344:Autopsy; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology / Q000821:virology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006509:Hepatitis B / Q000150:complications / Q000235:genetics / Q000473:pathology; D006515:Hepatitis B virus / Q000235:genetics / Q000472:pathogenicity; D006801:Humans; D053539:Keratin-19 / Q000096:biosynthesis* / Q000235:genetics; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology / Q000821:virology; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells; D019006:Neural Cell Adhesion Molecules / Q000096:biosynthesis / Q000235:genetics; D000509:alpha-Fetoproteins / Q000096:biosynthesis
chemical_list: D014408:Biomarkers, Tumor; D053539:Keratin-19; D019006:Neural Cell Adhesion Molecules; D000509:alpha-Fetoproteins