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

Purpose: To evaluate nuclear hypoxia-inducible factor 1 alpha (HIF-1 alpha) 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-1 alpha overall expression score was defined as high percentage and intensity staining and thus score > 1.33. Univariate analysis was performed for HIF-1 alpha 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-1 alpha expression, and 45 patients (46%) had low HIF-1 alpha expression. High HIF-1 alpha expression was significantly associated with DR (P = .03), and low HIF-1 alpha expression was significantly associated with isolated LR (P = .03). On multivariate logistic regression analysis, high HIF-1 alpha 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-1 alpha score >= 2.5 demonstrated a specificity of 100% for DR. Conclusions: High HIF-1 alpha expression is a significant predictor of distant failure versus isolated local failure in patients undergoing resection of pancreatic adenocarcinoma. Expression of HIF-1 alpha may have utility in determining candidates for adjuvant local radiation therapy and systemic chemotherapy. (C) 2015 Elsevier Inc.