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


METHODS
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.
Ailawadhi
Sikander
S
Department of Medicine, Roswell Park Cancer Institute, Buffalo, New York, USA.
Nagase
Hiroki
H
Khoury
Thaer
T
Yu
Jihnhee
J
Tan
Dongfeng
D
Black
Jennifer
J
Brattain
Michael
M
Javle
Milind
M
D000328:Adult; D000368:Aged; D001650:Bile Duct Neoplasms / Q000378:metabolism*; D001653:Bile Ducts, Intrahepatic; D018281:Cholangiocarcinoma / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010455:Peptides / Q000502:physiology*; D000071165:Trefoil Factor-3
D010455:Peptides; C082495:TFF3 protein, human; D000071165:Trefoil Factor-3; D048049:Extracellular Signal-Regulated MAP Kinases