Downregulated P1 promoter-driven hepatocyte nuclear factor-4alpha expression in human colorectal carcinoma is a new prognostic factor against liver metastasis

Pathol Int. 2007 Feb;57(2):82-90. doi: 10.1111/j.1440-1827.2006.02061.x.


Liver metastases are the most critical prognostic factors for patients with colorectal carcinomas (CRC). It has been reported that the dysregulation of hepatocyte nuclear factor-4alpha (HNF4alpha) expression is linked to the development of CRC, gastric cancer and hepatocellular carcinoma. The purpose of the present paper was to examine the P1 and P2 promoter-driven HNF4alpha (P1 and P2) expression in surgically resected CRC. Immunohistochemically, P1, P2, MUC1 and CD10 expression were evaluated in 63 cases of primary CRC. Positive staining with P1, P2, MUC1 and CD10 antibodies were observed in 37 (59%), 63 (100%), 42 (67%) and 27 (43%) cases, respectively. Loss or decreased P1 expression was observed with respect to the depth of the tumor invasion. The frequency of P1-positive expression in Dukes' C and D tumors was significantly lower than that in Dukes' A and B tumors. There was a relationship between the loss of P1 expression and metachronous liver metastases, and the survival rate of the P1-negative patients without liver metastasis at the time of the primary CRC resection tended to be worse than that of the P1-positive patients. These findings suggest that downregulation of P1 expression is involved in tumor metastasis and a worse prognosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma / diagnosis
  • Adenocarcinoma / metabolism*
  • Adenocarcinoma / pathology
  • Adenocarcinoma, Mucinous / metabolism*
  • Adenocarcinoma, Mucinous / pathology
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Colorectal Neoplasms / diagnosis
  • Colorectal Neoplasms / metabolism*
  • Colorectal Neoplasms / pathology
  • Disease Progression
  • Down-Regulation / physiology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hepatocyte Nuclear Factor 4 / genetics
  • Hepatocyte Nuclear Factor 4 / metabolism*
  • Humans
  • Liver Neoplasms / diagnosis
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / secondary*
  • Male
  • Middle Aged
  • Mucin-1 / genetics
  • Mucin-1 / metabolism
  • Neprilysin / genetics
  • Neprilysin / metabolism
  • Prognosis
  • Promoter Regions, Genetic / genetics
  • Promoter Regions, Genetic / physiology


  • Biomarkers, Tumor
  • HNF4A protein, human
  • Hepatocyte Nuclear Factor 4
  • Mucin-1
  • Neprilysin