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Pronecrotic mixed lineage kinase domain‐like protein expression is a prognostic biomarker in patients with early‐stage resected pancreatic adenocarcinoma
Author(s) -
Colbert Lauren E.,
Fisher Sarah B.,
Hardy Claire W.,
Hall William A.,
Saka Burcu,
Shelton Joseph W.,
Petrova Aleksandra V.,
Warren Matthew D.,
Pantazides Brooke G.,
Gandhi Khanjan,
Kowalski Jeanne,
Kooby David A.,
ElRayes Bassel F.,
Staley Charles A.,
Adsay N. Volkan,
Curran Walter J.,
Landry Jerome C.,
Maithel Shishir K.,
Yu David S.
Publication year - 2013
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/cncr.28144
Subject(s) - medicine , proportional hazards model , confidence interval , pancreatic cancer , adenocarcinoma , gastroenterology , oncology , chemotherapy , hazard ratio , survival analysis , stage (stratigraphy) , cancer , biology , paleontology
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. Cancer 2013;119:3148–3155 . © 2013 American Cancer Society .