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

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

Research output: Contribution to journalArticle

2 Citations (Scopus)

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 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
JournalHepato-Gastroenterology
Volume54
Issue number77
StatePublished - Jul 1 2007

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Cholangiocarcinoma
Extracellular Signal-Regulated MAP Kinases
Biliary Tract Neoplasms
Epidemiology
Cytoprotection
Trefoil Factor-3
Mucins
Liver Neoplasms
Phosphatidylinositol 3-Kinases
Colorectal Neoplasms
Epithelium
Biomarkers
Immunohistochemistry
Monoclonal Antibodies
Phenotype

Keywords

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

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Ailawadhi, S., Nagase, H., Khoury, T., Yu, J., Tan, D., Black, J. D., ... Javle, M. (2007). Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma. Hepato-Gastroenterology, 54(77), 1339-1344.

Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma. / Ailawadhi, Sikander; Nagase, Hiroki; Khoury, Thaer; Yu, Jihnhee; Tan, Dongfeng; Black, Jennifer D; Brattain, Michael G; Javle, Milind.

In: Hepato-Gastroenterology, Vol. 54, No. 77, 01.07.2007, p. 1339-1344.

Research output: Contribution to journalArticle

Ailawadhi, S, Nagase, H, Khoury, T, Yu, J, Tan, D, Black, JD, Brattain, MG & Javle, M 2007, 'Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma', Hepato-Gastroenterology, vol. 54, no. 77, pp. 1339-1344.
Ailawadhi, Sikander ; Nagase, Hiroki ; Khoury, Thaer ; Yu, Jihnhee ; Tan, Dongfeng ; Black, Jennifer D ; Brattain, Michael G ; Javle, Milind. / Intestinal trefoil factor (TFF-3) and extracellular signal-regulated kinase (ERK) in cholangiocarcinoma. In: Hepato-Gastroenterology. 2007 ; Vol. 54, No. 77. pp. 1339-1344.
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AU - Ailawadhi, Sikander

AU - Nagase, Hiroki

AU - Khoury, Thaer

AU - Yu, Jihnhee

AU - Tan, Dongfeng

AU - Black, Jennifer D

AU - Brattain, Michael G

AU - Javle, Milind

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N2 - 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.

AB - 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.

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