title: Osteopontin splice variant as a potential marker for metastatic disease in pancreatic adenocarcinoma.
abstract: OBJECTIVE
  Osteopontin (OPN) is a phosphoprotein that activates pathways that induce cancer cell survival and metastasis. Our aim was to examine the expression pattern of OPN splice variants a, b, and c in fine-needle aspirates and to determine their correlation with stage-adjusted pancreatic ductal adenocarcinoma (PDA) survival.
  
  
  METHODS
  Endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA) was performed in patients with solid pancreatic masses. The tissue was collected and analyzed for the expression of OPN isoforms by reverse transcription-polymerase chain reaction. Survival curves of stages and overexpression of OPN splice variants (a, b, c) were estimated according to the Kaplan-Meier and the log-rank test.
  
  
  RESULTS
  EUS-FNA was performed in 46 patients with solid pancreatic lesions (40 PDA and 6 chronic pancreatitis). OPNa was highly expressed in 39/40 (98%), OPNb in 24/40 (60%), while OPNc was present in 10/40 (25%) of PDA samples. The median survival was lower in patients whose fine-needle aspiration (FNA) samples expressed OPNb than those without (406 days vs 749 days, P = 0.049). There was no significant difference in survival in patients with OPNc. Cox proportional hazard model demonstrated that OPNb expression had a trend toward decrease overall survival (P = 0.06), with these patients having a hazard of death three times higher than those without. OPNc was found to significantly correlate with metastatic disease (P = 0.009) in PDA patients.
  
  
  CONCLUSIONS
  Our data show for the first time that in FNA samples, there is a strong association between OPNc and presence of metastasis in PDA, and OPNb and poor survival.
authors.affiliation: Department of Internal Medicine, Division of Gastroenterology, Thomas Jefferson University, Philadelphia, Pennsylvania, USA.
authors.forename: Ali A
authors.initials: AA
authors.lastname: Siddiqui
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Jones
authors.forename: Darren
authors.initials: D
authors.lastname: Andrade
authors.forename: Apeksha
authors.initials: A
authors.lastname: Shah
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Kowalski
authors.forename: David E
authors.initials: DE
authors.lastname: Loren
authors.forename: Galina
authors.initials: G
authors.lastname: Chipitsyna
authors.forename: Hwyda A
authors.initials: HA
authors.lastname: Arafat
mesh_terms: D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D044963:Biopsy, Fine-Needle; D019160:Endosonography; D005260:Female; D015870:Gene Expression; D056726:Genetic Association Studies; D014644:Genetic Variation; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D009362:Neoplasm Metastasis; D053495:Osteopontin / Q000235:genetics* / Q000378:metabolism*; D010190:Pancreatic Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate
chemical_list: D014408:Biomarkers, Tumor; D020033:Protein Isoforms; D053495:Osteopontin
keywords: cytology; fine-needle aspirates; osteopontin; pancreatic cancer