Intestinal Trefoil Factor (TFF3) expression and correlation with other signalling proteins in cholangiocarcinoma

Abstract

4137 Background: The mucin-associated trefoil factor (TFF) peptides are integral to cytoprotection and mucosal repair in the gastrointestinal tract. Existing literature supports the role of TFF in both, tumor suppression and tumor progression. TFF-3 is associated with an invasive phenotype and is over expressed in hepatolithiasis, gastric and hepatocellular carcinomas. TFF-mediated tumor progression involves resistance to apoptosis, angiogenesis, motogenic function and transactivation of EGFR, AKT, COX-2, and MAPK-signaling pathways. Methods: Twenty-four consecutive cases of cholangiocarcinoma treated from 1996–2002 were studied. Immunohistochemistry was performed using a monoclonal antibody to TFF-3. Sections were stained for biomarkers to assess co- expression of other signaling proteins including EGFR (Zymed), pEGFR (Santa Cruz), MAPK (Cell Signaling), pMAPK (Santa Cruz), AKT (Santa Cruz), pAKT (Cell Signaling) and COX-2 (DAKO). Clinical data were obtained per IRB approved protocol. Results: Median age was 67 years (range 35–77). There were 15 females and 9 males with a SEER (Surveillance, Epidemiology and End Results) staging of local in 1, regional in 15 and distant in 8. Treatments included chemotherapy (n=3), surgery (n=8), combined (n=11, 1 radiation + surgery, 5 chemotherapy + surgery and 5 all three) or no therapy (n=2). TFF-3 expression was positive in 19 samples. There were no significant associations between TFF-3 expression and sex, stage, grade, survival or SEER score. MAPK in tumor had a borderline positive association with pAKT (tau = 0.328, p = 0.0535) and a borderline negative correlation with TFF-3 [p=0.0588 (exact test), 0.059 (Pearson)]. Conclusions: TFF-3, COX-2, AKT and MAPK are commonly expressed in biliary cancers. Evaluation of co- expression and linkages between these signaling proteins may provide insight into pathogenesis of these cancers and suggest future targets for intervention. No significant financial relationships to disclose.