High nuclear hypoxia-inducible factor 1 alpha expression is a predictor of distant recurrence in patients with resected pancreatic adenocarcinoma Journal Article


Authors: Colbert, L. E.; Fisher, S. B.; Balci, S.; Saka, B.; Chen, Z.; Kim, S.; El-Rayes, B. F.; Adsay, N. V.; Maithel, S. K.; Landry, J. C.; Curran, W. J. Jr
Article Title: High nuclear hypoxia-inducible factor 1 alpha expression is a predictor of distant recurrence in patients with resected pancreatic adenocarcinoma
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. © 2015 Elsevier Inc. All rights reserved.
Keywords: immunohistochemistry; adult; cancer survival; human tissue; protein expression; aged; major clinical study; clinical feature; cancer recurrence; adjuvant therapy; cancer adjuvant therapy; cancer patient; cancer radiotherapy; neoadjuvant therapy; chemotherapy; outcome assessment; follow up; lymph node metastasis; antineoplastic agent; disease association; retrospective study; distant metastasis; confidence interval; pancreas adenocarcinoma; pancreatic adenocarcinoma; metastasis potential; cancer tissue; patient treatment; regression analysis; hypoxia inducible factor 1alpha; pathologist; local metastasis; predictive value; gastrointestinal radiography; progressive disease; hypoxia-inducible factor 1; diagnostic test accuracy study; cancer prognosis; adjuvant chemoradiotherapy; immunohistochemical staining; methods and materials; human; priority journal; article; multivariate logistic regressions
Journal Title: International Journal of Radiation Oncology, Biology, Physics
Volume: 91
Issue: 3
ISSN: 0360-3016
Publisher: Elsevier Inc.  
Date Published: 2015-03-01
Start Page: 631
End Page: 639
Language: English
DOI: 10.1016/j.ijrobp.2014.11.004
PROVIDER: scopus
PUBMED: 25596110
PMCID: PMC5746186
DOI/URL:
Notes: Export Date: 2 April 2015 -- Source: Scopus
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