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

Sikander Ailawadhi, Hiroki Nagase, Thaer Khoury, Jihnhee Yu, Dongfeng Tan, Jennifer Black, Michael Brattain, Milind Javle

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


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 ρ= -0.3988, p=0.0588). Conclusions: TFF-3 is commonly expressed in biliary cancers and may have a negative reciprocal relationship with Erk expression.

Original languageEnglish (US)
Pages (from-to)1339-1344
Number of pages6
Issue number77
StatePublished - Jul 2007


  • Cholangiocarcinoma
  • Epidermal Growth Factor Receptor (EGFR)
  • Mitogen Activated Protein Kinase (MAPK/Erk)
  • Signaling proteins
  • Trefoil Factor

ASJC Scopus subject areas

  • Hepatology
  • Gastroenterology


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