Nuclear Hypoxia-Inducible Factor 1 Alpha as a Predictor of Recurrence Pattern and Overall Survival in Resected Pancreatic Adenocarcinoma Público
Colbert, Lauren Elizabeth (2014)
Published
Abstract
Purpose:
Nuclear Hypoxia-Inducible Factor 1 Alpha (HIF1a) has been
implicated in development of cancer metastases. The goal of this
analysis was to evaluate HIF1a expression as a prognostic factor
for overall survival (OS), distant recurrence (DR) and local
recurrence (LR) following resection for pancreatic adenocarcinoma
(PAC).
Methods:
Specimens were collected from 98 patients with PAC who underwent
resection without neoadjuvant therapy between January 2000 and
December 2011 at one institution. Immunohistochemical (IHC)
staining was performed using anti-HIF1a antibody and scored using a
previously defined scoring system by an independent pathologist
blinded to patient outcomes. Univariate analysis was used to
compare HIF1a scores for LR and DR groups and for OS. Multivariate
logistic regression was used to determine predictors of LR and DR.
A receiver operating characteristic (ROC) curve was conducted for
predictive power of HIF1a expression on DR.
Results:
8 (8%) patients demonstrated isolated LR, 26 (26.5%) patients had
isolated DR, and 13 patients had both LR and DR. 53 (54%) patients
had high HIF1a expression and 45 (46%) patients had low HIF1a
expression. High HIF1a expression was significantly associated with
DR (p=0.03) and low HIF1a expression was significantly associated
with isolated LR (p=.02). In multivariate logistic regression
analysis adjusting for nodal status, margin status, tumor grade,
perineural invasion, lymphovascular invasion and use of adjuvant
therapy, high HIF1a was the only significant predictor of DR
(OR=3.10 [95% CI 1.18-8.10]; p=.02). In patients with a recurrence,
the AUC of high HIF1a score for DR was 74.8%. A HIF1a score ≥
2.5 demonstrated a specificity of 100% for DR in these
patients.
Conclusions:
High HIF1a expression is a predictor of distant failure versus
isolated local failure in patients undergoing resection of
pancreatic adenocarcinoma. HIF1a expression may have utility as a
clinical decision-making tool to determine candidates for adjuvant
local therapy and systemic chemotherapy.
Table of Contents
TABLE OF CONTENTS
INTRODUCTION & BACKGROUND...1
METHODS...3
RESULTS...8
DISCUSSION & CONCLUSIONS...11
REFERENCES...14
TABLES 1-8...20
FIGURES 1-3...26
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