Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors.

Philip R de Reuver, Shreya Mehta, Preetjote Gill, Juliana Andrici, Lisa D'Urso, Adele Clarkson, Anubhav Mittal, Thomas J Hugh, Jaswinder S Samra, Anthony J Gill

Journal of the American College of Surgeons 2016 Mar

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Forkhead box protein p3-positive (FoxP3(+)) regulatory T cells (Tregs) suppress host T-cell-mediated immune responses, limit surveillance against cancers, and have been associated with a poor prognosis. This study aims to identify the prognostic significance of FoxP3(+) Tregs in pancreatic neuroendocrine tumors (PNETs). Patients diagnosed with PNETs between 1992 and 2014 (n = 101) were included in this retrospective analysis. Clinical data, histopathology, and expression of FoxP3(+) Tregs and Ki-67 by immunohistochemistry were assessed. The association of these factors with survival was tested by log-rank test and in additional multivariable analysis. A total of 101 patients were included in this study. Mean age was 58.0 years (range 18 to 87 years) and median tumor size was 25 mm (range 8 to 160 mm). The degree of infiltration of tumor by FoxP3(+) Tregs was graded as 0 (n = 75), 1 (n = 15), or 2 (n = 11). Median follow-up was 50 months (interquartile range 123 months; Q1 = 20 months and Q3 = 123 months). In univariate analyses, patient age older than 57 years, TNM stage III or IV, tumor size >25 mm, Ki-67 labeling index >20, and a high number of FoxP3(+) tumor-infiltrating lymphocytes were significantly associated with poorer overall survival. In multivariable analyses, FoxP3(+) expression score of 2 (hazard ratio = 6.9; 95% CI 1.4-34.4) was the only statistically significant predictor for overall mortality. FoxP3(+) Treg expression is an independent prognostic factor in patients with PNETs, associated with statistically significant shorter overall survival. There is a role for additional research into the immune-mediated role of FoxP3(+) Tregs in PNETs. Copyright © 2016 American College of Surgeons. Published by Elsevier Inc. All rights reserved.

Citation

Philip R de Reuver, Shreya Mehta, Preetjote Gill, Juliana Andrici, Lisa D'Urso, Adele Clarkson, Anubhav Mittal, Thomas J Hugh, Jaswinder S Samra, Anthony J Gill. Immunoregulatory Forkhead Box Protein p3-Positive Lymphocytes Are Associated with Overall Survival in Patients with Pancreatic Neuroendocrine Tumors. Journal of the American College of Surgeons. 2016 Mar;222(3):281-7