High Nuclear Hypoxia-Inducible Factor 1 Alpha Expression Is a Predictor of Distant Recurrence in Patients With Resected Pancreatic Adenocarcinoma

• Type of Material: Article
• Authors: Lauren E. Colbert, Emory University; Sarah B. Fisher, Emory University; Serdar Balci, Emory University; Burcu Saka, Emory University; Zhengjia Chen, Emory University; Sungjin Kim, Emory University; Bassel El-Rayes, Emory University; Nazmi Adsay, Emory University; Shishir Kumar Maithel, Emory University; Jerome C Landry, Emory University; Walter J Curran, Emory University
• Language: English
• Date: 2015-03-01
• Publisher: Elsevier
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2015 Elsevier Inc. All rights reserved.
• Final Published Version (URL): http://dx.doi.org/10.1016/j.ijrobp.2014.11.004
• Title of Journal or Parent Work: International Journal of Radiation Oncology - Biology - Physics
• ISSN: 0360-3016
• Volume: 91
• Issue: 3
• Start Page: 631
• End Page: 639
• Grant/Funding Information: Supported by the National Center for Advancing Translational Sciences of the National Institutes of Health under Award Numbers ULl TR000454 to LEC and SBF and TLlTR000456 to LEC.; The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.
• Keywords: Science & Technology; CANCER; INHIBITOR PX-478; Radiology, Nuclear Medicine & Medical Imaging; PROGNOSIS; FACTOR 1-ALPHA; Life Sciences & Biomedicine; HEPATOCELLULAR-CARCINOMA; Oncology; REPORTING RECOMMENDATIONS; DUCTAL ADENOCARCINOMAS; MARKER; CHEMOTHERAPY; FACTOR-I ALPHA
• Research Categories: Health Sciences, Oncology; Health Sciences, Pathology

Abstract

Purpose To evaluate nuclear hypoxia-inducible factor 1α (HIF-1α) expression as a prognostic factor for distant recurrence (DR) and local recurrence (LR) after pancreatic adenocarcinoma resection. Methods and Materials Tissue specimens were collected from 98 patients with pancreatic adenocarcinoma who underwent resection without neoadjuvant therapy between January 2000 and December 2011. Local recurrence was defined as radiographic or pathologic evidence of progressive disease in the pancreas, pancreatic bed, or associated nodal regions. Distant recurrence was defined as radiographically or pathologically confirmed recurrent disease in other sites. Immunohistochemical staining was performed and scored by an independent pathologist blinded to patient outcomes. High HIF-1α overall expression score was defined as high percentage and intensity staining and thus score > 1.33. Univariate analysis was performed for HIF-1α score with LR alone and with DR. Multivariate logistic regression was used to determine predictors of LR and DR. Results Median follow-up time for all patients was 16.3 months. Eight patients (8%) demonstrated isolated LR, 26 patients (26.5%) had isolated DR, and 13 patients had both LR and DR. Fifty-three patients (54%) had high HIF-1α expression, and 45 patients (46%) had low HIF-1α expression. High HIF-1α expression was significantly associated with DR (P=.03), and low HIF-1α expression was significantly associated with isolated LR (P=.03). On multivariate logistic regression analysis, high HIF-1α was the only significant predictor of DR (odds ratio 2.46 [95% confidence interval 1.06-5.72]; P=.03). In patients with a known recurrence, an HIF-1α score ≥2.5 demonstrated a specificity of 100% for DR. Conclusions High HIF-1α expression is a significant predictor of distant failure versus isolated local failure in patients undergoing resection of pancreatic adenocarcinoma. Expression of HIF-1α may have utility in determining candidates for adjuvant local radiation therapy and systemic chemotherapy.