title: Plectin-1 as a novel biomarker for pancreatic cancer.
abstract: OBJECTIVE
  We are in great need of specific biomarkers to detect pancreatic ductal adenocarcinoma (PDAC) at an early stage, ideally before invasion. Plectin-1 (Plec1) was recently identified as one such biomarker. However, its suitability as a specific biomarker for human pancreatic cancer, and its usability as an imaging target, remain to be assessed.
  
  
  METHODS
  Specimens of human PDAC, chronic pancreatitis, and normal pancreata were evaluated by immunohistochemistry and Western blot analysis. To validate Plec1 as an imaging target, Plec1-targeting peptides (tPTP) were used as a contrast agent for single photon emission computed tomography in an orthotopic and liver metastasis murine model of PDAC.
  
  
  RESULTS
  Plec1 expression was noted to be positive in all PDACs but negative in benign tissues. Plec1 expression increases during pancreatic carcinogenesis. It was found to be misexpressed in only 0% to 3.85% of early PDAC precursor lesions (PanIN I/II) but in 60% of PanIN III lesions. Plec1 expression was further noted to be retained in all metastatic foci assayed and clearly highlighted these metastatic deposits in lymph nodes, liver, and peritoneum. In vivo imaging using tPTP specifically highlighted the primary and metastatic tumors. Biodistribution studies performed after imaging show that the primary pancreatic tumors and liver metastases retained 1.9- to 2.9-fold of tPTP over normal pancreas and 1.7-fold over normal liver.
  
  
  CONCLUSIONS
  Plec1 is the first biomarker to identify primary and metastatic PDAC by imaging and may also detect preinvasive PanIN III lesions. Strategies designed to image Plec1 could therefore improve detection and staging.
authors.affiliation: Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts 02114-2622, USA.
authors.forename: Dirk
authors.initials: D
authors.lastname: Bausch
authors.forename: Stephanie
authors.initials: S
authors.lastname: Thomas
authors.forename: Mari
authors.initials: M
authors.lastname: Mino-Kenudson
authors.forename: Castillo Carlos
authors.initials: CC
authors.lastname: Fernández-del
authors.forename: Todd W
authors.initials: TW
authors.lastname: Bauer
authors.forename: Mark
authors.initials: M
authors.lastname: Williams
authors.forename: Andrew L
authors.initials: AL
authors.lastname: Warshaw
authors.forename: Sarah P
authors.initials: SP
authors.lastname: Thayer
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Kelly
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000032:analysis*; D021441:Carcinoma, Pancreatic Ductal / Q000175:diagnosis*; D003287:Contrast Media; D006801:Humans; D008113:Liver Neoplasms / Q000556:secondary; D051379:Mice; D008819:Mice, Nude; D010179:Pancreas / Q000737:chemistry; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000473:pathology; D010195:Pancreatitis / Q000378:metabolism; D051190:Plectin / Q000032:analysis*; D015899:Tomography, Emission-Computed, Single-Photon / Q000379:methods
chemical_list: D014408:Biomarkers, Tumor; D003287:Contrast Media; C495332:PLEC protein, human; D051190:Plectin