High mobility group AT-hook 2 is overexpressed in hepatoblastoma

Hum Pathol. 2013 May;44(5):802-10. doi: 10.1016/j.humpath.2012.08.003. Epub 2012 Nov 5.

Abstract

Hepatoblastoma is the most frequent malignant hepatic tumor in children. Expression of high mobility group AT-hook 2, an architectural nuclear factor and marker for hepatic progenitor cells, has not been studied in detail in hepatocellular neoplasms. Immunohistochemical stains using antibodies against high mobility group AT-hook 2, β-catenin, glypican-3, p53, and Ki-67 were performed in 15 hepatoblastomas, 15 fibrolamellar hepatocellular carcinomas, 34 hepatocellular carcinomas (12, ≤30 years old; 22, >30 years old), and 22 hepatic adenomas. High mobility group AT-hook 2 was expressed in all 15 hepatoblastomas, including all fetal and embryonal components, significantly higher than in 41.7% (5/12) of hepatocellular carcinomas of 30 years or younger (P = .001) and in 9% (2/22) of hepatocellular carcinomas of older than 30 years (P < .001). Aberrant β-catenin expression was detected in 80% (12/15) of hepatoblastomas, 41.6% (5/12) of hepatocellular carcinomas of 30 years or younger, and 18.2% (4/22) of hepatocellular carcinomas of older than 30 years. All 15 fibrolamellar hepatocellular carcinomas and 22 hepatic adenomas were negative for high mobility group AT-hook 2 or β-catenin. High mobility group AT-hook 2 and β-catenin expression correlated positively (P = .017; τ = 0.522) in 34 hepatocellular carcinomas. β-Catenin and glypican-3 exhibited a distinct spatial distribution within hepatoblastomas; glypican-3 was more frequently expressed in fetal components (P = .007), whereas β-catenin tended to be more frequently expressed in embryonal components (P = .062). In conclusion, high mobility group AT-hook 2 is expressed in all hepatoblastomas and could be used as a sensitive marker in their diagnosis. High mobility group AT-hook 2 was also expressed in a subset of hepatocellular carcinomas in association with β-catenin expression; this might represent a subtype of hepatocellular carcinoma with hepatic progenitor cell differentiation.

MeSH terms

  • Adenoma, Liver Cell / metabolism
  • Adolescent
  • Adult
  • Biomarkers, Tumor
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology
  • Child
  • Child, Preschool
  • Female
  • Glypicans / biosynthesis
  • HMGA2 Protein / biosynthesis*
  • Hepatoblastoma / metabolism*
  • Hepatoblastoma / pathology
  • Humans
  • Infant
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / pathology
  • Male
  • Middle Aged
  • beta Catenin / biosynthesis

Substances

  • Biomarkers, Tumor
  • Glypicans
  • HMGA2 Protein
  • beta Catenin

Supplementary concepts

  • Fibrolamellar hepatocellular carcinoma