Ehehalt, Florian and Ruemmele, Petra and Kersting, Stephan and Lang-Schwarz, Corinna and Rueckert, Felix and Hartmann, Arndt and Dietmaier, Wolfgang and Terracciano, Luigi and Aust, Daniela E. and Jahnke, Beatrix and Saeger, Hans-Detlev and Pilarsky, Christian and Gruetzmann, Robert (2011) Hepatocyte Nuclear Factor (HNF) 4 alpha Expression Distinguishes Ampullary Cancer Subtypes and Prognosis After Resection. ANNALS OF SURGERY, 254 (2). pp. 302-310. ISSN 0003-4932,
Full text not available from this repository. (Request a copy)Abstract
Objective: To investigate biological differences and prognostic indicators of different ampullary cancer (AC) subtypes. Background: AC is associated with a favorable prognosis compared with other periampullary carcinomas. Aside from other prognostic factors, the histological origin of AC may determine survival. Specifically, the pancreatobiliary subtype of AC displays worse prognosis compared with the intestinal subtype. However, knowledge of inherent molecular characteristics of different periampullary tumors and their effects on prognosis has been limited. Methods: Gene expression profiling was used to screen for differential gene expression between 6 PDAC cases and 12 AC cases. Among others, hepatocyte nuclear factor 4 alpha (HNF4 alpha) mRNA overexpression was observed in AC cases. Nuclear HNF4 alpha protein expression was assessed using tissue microarrays consisting of 99 individual AC samples. The correlation of HNF4 alpha expression with clinicopathological data (n = 99) and survival (n = 84) was assessed. Results: HNF4 alpha mRNA is 7.61-fold up-regulated in AC compared with that in PDAC. Bioinformatics analyses indicated its key role in dysregulated signaling pathways. Nuclear HNF4 alpha expression correlates with histological subtype, grading, CDX2 positivity, MUC1 negativity and presence of adenomatous components in the carcinoma. The presence of HNF4 alpha is a univariate predictor of survival in AC mean survival (50 months versus 119 months, P = 0.002). Multivariate analysis revealed that HNF4 alpha negativity (HR = 17.95, 95% CI: 2.35-136.93, P = 0.005) and lymph node positivity (HR = 3.33, 95% CI: 1.36-8.18, P = 0.009) are independent negative predictors of survival. Conclusions: Immunohistochemical determination of HNF4 alpha expression is an effective tool for distinguishing different AC subtypes. Similarly, HNF4 alpha protein expression is an independent predictor of favorable prognosis in carcinoma of the papilla of Vater and may serve for risk stratification after curative resection.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | ADENOMA-CARCINOMA SEQUENCE; MICROSATELLITE INSTABILITY; VATER; PAPILLA; ADENOCARCINOMA; NEOPLASMS; SURVIVAL; PANCREATICOBILIARY; DIFFERENTIATION; TUMORS; |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 03 Jun 2020 09:17 |
| Last Modified: | 03 Jun 2020 09:17 |
| URI: | https://pred.uni-regensburg.de/id/eprint/20478 |
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