1. Hepatocyte Nuclear Factor (HNF) 4α Expression Distinguishes Ampullary Cancer Subtypes and Prognosis After Resection
- Author
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Felix Rückert, Hans-Detlev Saeger, Christian Pilarsky, Daniela Aust, Stephan Kersting, Beatrix Jahnke, Robert Grützmann, Corinna Lang-Schwarz, Wolfgang Dietmaier, Arndt Hartmann, Petra Rümmele, Luigi Terracciano, and Florian Ehehalt
- Subjects
Adult ,Ampulla of Vater ,Lymphatic metastasis ,Pathology ,medicine.medical_specialty ,Common Bile Duct Neoplasms ,Kaplan-Meier Estimate ,Adenocarcinoma ,Ampullary cancer ,Resection ,Immunoenzyme Techniques ,Humans ,Medicine ,RNA, Messenger ,Survival rate ,Genetic Association Studies ,Aged ,Neoplasm Staging ,Oligonucleotide Array Sequence Analysis ,Proportional Hazards Models ,Regulation of gene expression ,business.industry ,Gene Expression Profiling ,Middle Aged ,Prognosis ,Up-Regulation ,Gene Expression Regulation, Neoplastic ,Survival Rate ,Gene expression profiling ,Hepatocyte nuclear factors ,Hepatocyte Nuclear Factor 4 ,Lymphatic Metastasis ,Cancer research ,Surgery ,Neoplasm staging ,business - Abstract
To investigate biological differences and prognostic indicators of different ampullary cancer (AC) subtypes.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.Gene expression profiling was used to screen for differential gene expression between 6 PDAC cases and 12 AC cases. Among others, hepatocyte nuclear factor 4α (HNF4α) mRNA overexpression was observed in AC cases. Nuclear HNF4α protein expression was assessed using tissue microarrays consisting of 99 individual AC samples. The correlation of HNF4α expression with clinicopathological data (n = 99) and survival (n = 84) was assessed.HNF4α 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 HNF4α expression correlates with histological subtype, grading, CDX2 positivity, MUC1 negativity and presence of adenomatous components in the carcinoma. The presence of HNF4α is a univariate predictor of survival in AC mean survival (50 months versus 119 months, P = 0.002). Multivariate analysis revealed that HNF4α 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.Immunohistochemical determination of HNF4α expression is an effective tool for distinguishing different AC subtypes. Similarly, HNF4α 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.
- Published
- 2011
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