Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma

Hepatogastroenterology. 2007 Jul-Aug;54(77):1339-44.

Abstract

Background/aims: The mucin-associated trefoil factor (TFF) peptides are integral to cytoprotection. TFF-3 is aberrantly expressed in colorectal and hepatocellular cancer and associated with an invasive phenotype. TFF-3 is also expressed in normal biliary epithelium. However, its role in biliary cancers is unknown. The biological effects of TFFs may result from EGFR, PI3 kinase, COX-2 and STAT-mediated signaling. We investigated the expression of TFF-3, Erk, Akt, EGFR and COX-2 in biliary cancer.

Methodology: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996-2002 were studied. Immunohistochemistry was performed using monoclonal antibodies to TFF-3, EGFR, pEGFR, Erk, pErk, Akt, pAkt and COX-2 using validated techniques. Kendall's tau (exact method) and Pearson correlation test were employed to investigate the associations between biomarkers.

Results: Median age was 67 years. Surveillance, Epidemiology and End Results (SEER) stage was local in 1, regional in 15 and distant in 8. TFF-3 expression was detected in 19 cases. There were no significant associations between TFF-3 expression and sex, stage, grade, survival or SEER score. Erk expression in the tumor showed a borderline, negative correlation with TFF-3 (Pearson's p= -0.3988, p = 0.0588).

Conclusions: TFF-3 is commonly expressed in biliary cancers and may have a negative reciprocal relationship with Erk expression.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Bile Duct Neoplasms / metabolism*
  • Bile Ducts, Intrahepatic*
  • Cholangiocarcinoma / metabolism*
  • Extracellular Signal-Regulated MAP Kinases / biosynthesis*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Peptides / physiology*
  • Trefoil Factor-3

Substances

  • Peptides
  • TFF3 protein, human
  • Trefoil Factor-3
  • Extracellular Signal-Regulated MAP Kinases