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 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. RESULTS: 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. CONCLUSIONS: 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.
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 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Jin He; Nita Ahuja; Martin A Makary; John L Cameron; Frederic E Eckhauser; Michael A Choti; Ralph H Hruban; Timothy M Pawlik; Christopher L Wolfgang Journal: HPB (Oxford) Date: 2013-03-08 Impact factor: 3.647
Authors: Marie-Claude Gingras; Kyle R Covington; David K Chang; Lawrence A Donehower; Anthony J Gill; Michael M Ittmann; Chad J Creighton; Amber L Johns; Eve Shinbrot; Ninad Dewal; William E Fisher; Christian Pilarsky; Robert Grützmann; Michael J Overman; Nigel B Jamieson; George Van Buren; Jennifer Drummond; Kimberly Walker; Oliver A Hampton; Liu Xi; Donna M Muzny; Harsha Doddapaneni; Sandra L Lee; Michelle Bellair; Jianhong Hu; Yi Han; Huyen H Dinh; Mike Dahdouli; Jaswinder S Samra; Peter Bailey; Nicola Waddell; John V Pearson; Ivon Harliwong; Huamin Wang; Daniela Aust; Karin A Oien; Ralph H Hruban; Sally E Hodges; Amy McElhany; Charupong Saengboonmee; Fraser R Duthie; Sean M Grimmond; Andrew V Biankin; David A Wheeler; Richard A Gibbs Journal: Cell Rep Date: 2016-01-21 Impact factor: 9.423
Authors: Yihui Chen; Michela Capello; Mayrim V Rios Perez; Jody V Vykoukal; David Roife; Ya'an Kang; Laura R Prakash; Hiroyuki Katayama; Ehsan Irajizad; Alia Fleury; Sammy Ferri-Borgogno; Dodge L Baluya; Jennifer B Dennison; Kim-Anh Do; Oliver Fiehn; Anirban Maitra; Huamin Wang; Paul J Chiao; Matthew H G Katz; Jason B Fleming; Samir M Hanash; Johannes F Fahrmann Journal: Mol Metab Date: 2021-12-28 Impact factor: 7.422
Authors: Michael J Overman; Jiexin Zhang; Scott Kopetz; Michael Davies; Zhi-Qin Jiang; Jiang Zhi-Qin; Katherine Stemke-Hale; Petra Rümmele; Christian Pilarsky; Robert Grützmann; Stanley Hamilton; Rosa Hwang; James L Abbruzzese; Gauri Varadhachary; Bradley Broom; Huamin Wang Journal: PLoS One Date: 2013-06-11 Impact factor: 3.240
Authors: Jennifer K Plichta; Anjali S Godambe; Zachary Fridirici; Sherri Yong; James M Sinacore; Gerard J Abood; Gerard V Aranha Journal: HPB Surg Date: 2014-07-01
Authors: Zon Weng Lai; Louisa Bolm; Hannah Fuellgraf; Martin L Biniossek; Frank Makowiec; Ulrich Theodor Hopt; Martin Werner; Tobias Keck; Dirk Bausch; Claudio Sorio; Aldo Scarpa; Oliver Schilling; Peter Bronsert; Ulrich Friedrich Wellner Journal: BMC Cancer Date: 2016-03-08 Impact factor: 4.430