BACKGROUND: Mixed lineage kinase domain-like protein (MLKL) is a necrosome component mediating programmed necrosis that may be an important determinant of cancer cell death. The goal of the current study was to evaluate the prognostic value of MLKL expression in patients with pancreatic adenocarcinoma (PAC). METHODS: Tissue from 80 patients was collected from a prospectively maintained database of patients with PAC who underwent pancreaticoduodenectomy between January 2000 and October 2008. Immunohistochemistry analysis was performed and scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival (RFS) and overall survival (OS) for all patients and for patients receiving adjuvant chemotherapy. MLKL scores were correlated with RFS and OS using univariate and multivariate Cox regression analyses incorporating clinically relevant covariates. RESULTS: The median age of the patients was 63 years and 53% were men. Low MLKL expression was associated with decreased OS (6 months vs 17 months; P = .006). In the subset of 59 patients who received adjuvant chemotherapy, low MLKL expression was associated with decreased RFS (5 months vs 15 months; P = .006) and decreased OS (6 months vs 19 months; P < .0001). On multivariate analysis, low MLKL expression was associated with poor OS in all patients (hazards ratio, 4.6 [95% confidence interval, 1.6-13.8]; P = .006) and in patients receiving adjuvant chemotherapy (hazards ratio, 8.1 [95% confidence interval, 2.2-29.2]; P = .002). CONCLUSIONS: Low expression of MLKL is associated with decreased OS in patients with resected PAC and decreased RFS and OS in the subset of patients with resected PAC who receive adjuvant chemotherapy. The use of this biomarker in patients with PAC may provide important prognostic information.
BACKGROUND:Mixed lineage kinase domain-like protein (MLKL) is a necrosome component mediating programmed necrosis that may be an important determinant of cancer cell death. The goal of the current study was to evaluate the prognostic value of MLKL expression in patients with pancreatic adenocarcinoma (PAC). METHODS: Tissue from 80 patients was collected from a prospectively maintained database of patients with PAC who underwent pancreaticoduodenectomy between January 2000 and October 2008. Immunohistochemistry analysis was performed and scored using an established scoring system. Kaplan-Meier survival curves were generated for recurrence-free survival (RFS) and overall survival (OS) for all patients and for patients receiving adjuvant chemotherapy. MLKL scores were correlated with RFS and OS using univariate and multivariate Cox regression analyses incorporating clinically relevant covariates. RESULTS: The median age of the patients was 63 years and 53% were men. Low MLKL expression was associated with decreased OS (6 months vs 17 months; P = .006). In the subset of 59 patients who received adjuvant chemotherapy, low MLKL expression was associated with decreased RFS (5 months vs 15 months; P = .006) and decreased OS (6 months vs 19 months; P < .0001). On multivariate analysis, low MLKL expression was associated with poor OS in all patients (hazards ratio, 4.6 [95% confidence interval, 1.6-13.8]; P = .006) and in patients receiving adjuvant chemotherapy (hazards ratio, 8.1 [95% confidence interval, 2.2-29.2]; P = .002). CONCLUSIONS: Low expression of MLKL is associated with decreased OS in patients with resected PAC and decreased RFS and OS in the subset of patients with resected PAC who receive adjuvant chemotherapy. The use of this biomarker in patients with PAC may provide important prognostic information.
Authors: Helmut Oettle; Stefan Post; Peter Neuhaus; Klaus Gellert; Jan Langrehr; Karsten Ridwelski; Harald Schramm; Joerg Fahlke; Carl Zuelke; Christof Burkart; Klaus Gutberlet; Erika Kettner; Harald Schmalenberg; Karin Weigang-Koehler; Wolf-Otto Bechstein; Marco Niedergethmann; Ingo Schmidt-Wolf; Lars Roll; Bernd Doerken; Hanno Riess Journal: JAMA Date: 2007-01-17 Impact factor: 56.272
Authors: James J Farrell; Hany Elsaleh; Miguel Garcia; Raymond Lai; Ali Ammar; William F Regine; Ross Abrams; A Bowen Benson; John Macdonald; Carol E Cass; Adam P Dicker; John R Mackey Journal: Gastroenterology Date: 2008-10-07 Impact factor: 22.682
Authors: Christine A Iacobuzio-Donahue; Baojin Fu; Shinichi Yachida; Mingde Luo; Hisashi Abe; Clark M Henderson; Felip Vilardell; Zheng Wang; Jesse W Keller; Priya Banerjee; Joseph M Herman; John L Cameron; Charles J Yeo; Marc K Halushka; James R Eshleman; Marian Raben; Alison P Klein; Ralph H Hruban; Manuel Hidalgo; Daniel Laheru Journal: J Clin Oncol Date: 2009-03-09 Impact factor: 44.544
Authors: Renee D Paulsen; Deena V Soni; Roy Wollman; Angela T Hahn; Muh-Ching Yee; Anna Guan; Jayne A Hesley; Steven C Miller; Evan F Cromwell; David E Solow-Cordero; Tobias Meyer; Karlene A Cimprich Journal: Mol Cell Date: 2009-07-31 Impact factor: 17.970
Authors: Sarah B Fisher; Sameer H Patel; Pelin Bagci; David A Kooby; Bassel F El-Rayes; Charles A Staley; N Volkan Adsay; Shishir K Maithel Journal: Cancer Date: 2012-05-08 Impact factor: 6.860
Authors: Crystal S Seldon; Lauren E Colbert; William A Hall; Sarah B Fisher; David S Yu; Jerome C Landry Journal: World J Gastrointest Oncol Date: 2016-04-15
Authors: C Xu; M B Wallace; J Yang; L Jiang; Q Zhai; Y Zhang; C Hong; Y Chen; T S Frank; J A Stauffer; H J Asbun; M Raimondo; T A Woodward; Z Li; S Guha; L Zheng; M Li Journal: Curr Mol Med Date: 2014-03 Impact factor: 2.222