title: High nuclear hypoxia-inducible factor 1 alpha expression is a predictor of distant recurrence in patients with resected pancreatic adenocarcinoma.
abstract: OBJECTIVE
  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
  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.
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia; Winship Cancer Institute, Emory University, Atlanta, Georgia; Memorial Sloan-Kettering Cancer Center, New York, New York.
authors.forename: Lauren E
authors.initials: LE
authors.lastname: Colbert
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia.
authors.forename: Sarah B
authors.initials: SB
authors.lastname: Fisher
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Department of Pathology, Emory University, Atlanta, Georgia.
authors.forename: Serdar
authors.initials: S
authors.lastname: Balci
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Department of Pathology, Emory University, Atlanta, Georgia.
authors.forename: Burcu
authors.initials: B
authors.lastname: Saka
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia.
authors.forename: Zhengjia
authors.initials: Z
authors.lastname: Chen
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia.
authors.forename: Sungjin
authors.initials: S
authors.lastname: Kim
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Department of Hematology and Medical Oncology, Emory University, Atlanta, Georgia.
authors.forename: Bassel F
authors.initials: BF
authors.lastname: El-Rayes
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Department of Pathology, Emory University, Atlanta, Georgia; Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia.
authors.forename: N Volkan
authors.initials: NV
authors.lastname: Adsay
authors.affiliation: Winship Cancer Institute, Emory University, Atlanta, Georgia; Division of Surgical Oncology, Department of Surgery, Emory University, Atlanta, Georgia; Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia.
authors.forename: Shishir K
authors.initials: SK
authors.lastname: Maithel
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia; Winship Cancer Institute, Emory University, Atlanta, Georgia; Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia.
authors.forename: Jerome C
authors.initials: JC
authors.lastname: Landry
authors.affiliation: Department of Radiation Oncology, Emory University, Atlanta, Georgia; Winship Cancer Institute, Emory University, Atlanta, Georgia; Biostatistics and Bioinformatics Shared Resource, Emory University, Atlanta, Georgia. Electronic address: wcurran@emory.edu.
authors.forename: Walter J
authors.initials: WJ
authors.lastname: Curran
mesh_terms: D000230:Adenocarcinoma / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000556:secondary* / Q000601:surgery; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009363:Neoplasm Proteins / Q000378:metabolism*; D009364:Neoplasm Recurrence, Local; D010190:Pancreatic Neoplasms / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000601:surgery; D011379:Prognosis; D011859:Radiography; D012044:Regression Analysis; D012680:Sensitivity and Specificity
chemical_list: D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D009363:Neoplasm Proteins