Authors: Ru Chen, Sheng Pan, NIki A. Ottenhof, Roeland F. de Wilde, Christopher L. Wolfgang, Zhaoli Lane, Jane Post, Mary P. Bronner, Jürgen K. Willmann, Anirban Maitra and Teresa A. Brentnall

Ru Chen

Department of Medicine; University of Washington; Seattle, WA USA

Sheng Pan

Department of Medicine; University of Washington; Seattle, WA USA

NIki A. Ottenhof

Department of Pathology; Sol Goldman Pancreatic Cancer Research Center; The Johns Hopkins Medical Institutions; Baltimore, MD USA

Roeland F. de Wilde

Department of Pathology; Sol Goldman Pancreatic Cancer Research Center; The Johns Hopkins Medical Institutions; Baltimore, MD USA

Christopher L. Wolfgang

Department of Surgery; Sol Goldman Pancreatic Cancer Research Center; The Johns Hopkins Medical Institutions; Baltimore, MD USA

Zhaoli Lane

Henry Ford Hospital; Detroit, MI USA

Jane Post

Cleveland Clinic Foundation; Cleveland, OH USA

Mary P. Bronner

Division of Anatomic Pathology; University of Utah; Salt Lake City, UT USA

Jürgen K. Willmann

Department of Radiology; Stanford University; Stanford, CA USA

Anirban Maitra

Department of Pathology; Sol Goldman Pancreatic Cancer Research Center; The Johns Hopkins Medical Institutions; Baltimore, MD USA

Teresa A. Brentnall

Corresponding author: teribr@u.washington.edu
Department of Medicine; University of Washington; Seattle, WA USA

Abstract:
The overall 5 year survival rate for pancreatic ductal adenocarcinoma (i.e., PDAC) is a dismal 5%, although patients that have undergone surgical resection have a somewhat better survival rate of up to 20%. Very long-term survivors of PDAC (defined as patients with ≥ 10 year survival following apparently curative resection), on the other hand, are considerably less frequent. The molecular characteristics of very long-term survivors (VLTS) are poorly understood, but might provide novel insights into prognostication for this disease. In this study, a panel of five VLTS and stage-matched short-term survivors (STS, defined as disease-specific mortality within 14 months of resection) were identified, and quantitative proteomics was applied to comparatively profile tumor tissues from both cohorts. Differentially expressed proteins were identified in cancers from VLTS vs. STS patients. Specifically, the expression of galectin-1 was 2-fold lower in VLTS compared with STS tumors. Validation studies were performed by immunohistochemistry (IHC) in two additional cohorts of resected PDAC, including: 1) an independent cohort of VLTS and 2) a panel of sporadic PDAC with a considerable range of overall survival following surgery. Immunolabeling analysis confirmed that significantly lower expression of stromal galectin-1 was associated with VLTS (p = 0.02) and also correlated with longer survival in sporadic, surgically-treated PDAC cases (hazard ratio = 4.9, p = 0.002). The results from this study provide new insights to better understand the role of galectin-1 in PDAC survival, and might be useful for rendering prognostic information, and developing more effective therapeutic strategies aimed at improving survival.

Received: February 6, 2012; Accepted: May 22, 2012

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