title: Proteomic mucin profiling for the identification of cystic precursors of pancreatic cancer.
abstract: BACKGROUND
  Pancreatic cystic lesions (PCLs) are increasingly frequent radiological incidentalomas, with a considerable proportion representing precursors of pancreatic cancer. Better diagnostic tools are required for patients to benefit from this development.
  
  
  METHODS
  To evaluate whether cyst fluid mucin expression could predict malignant potential and/or transformation in PCLs, a proteomic method was devised and prospectively evaluated in consecutive patients referred to our tertiary center for endoscopic ultrasound-guided aspiration of cystic lesions from May 2007 through November 2008 (discovery cohort) and from December 2008 through October 2012 (validation cohort). Cytology and cyst fluid carcinoembryonic antigen (CEA; premalignancy > 192 ng/mL, malignancy > 1000 ng/mL) were routinely analyzed, and samples were further processed as follows: one-dimensional gel electrophoresis, excision of high-mass areas, tryptic digestion and nano-liquid chromatography-tandem mass spectrometry, with peptide identification by Mascot software and an in-house mucin database. All diagnostic evaluations were blinded to proteomics results. Histology was required to confirm the presence/absence of malignant transformation. All statistical tests were two-sided.
  
  
  RESULTS
  Proteomic mucin profiling proved statistically significantly more accurate (97.5%; 95% confidence interval [CI] = 90.3% to 99.6%) than cytology (71.4%; 95% CI = 59.8% to 80.9%; P < .001) and cyst fluid CEA (78.0%; 95% CI = 65.0% to 87.3%; P < .001) in identifying the 37 (out of 79; 46.8%) lesions with malignant potential (ie, premalignant or malignant tumors). The accuracy of proteomics was nearly identical (96.6% vs 98.0%) between the discovery (n = 29) and validation (n = 50) cohorts. Furthermore, mucin profiling predicted malignant transformation, present in 16 out of 29 (discovery cohort: 9, validation cohort: 20) lesions with available histology, with 89.7% accuracy (95% CI = 71.5% to 97.3%) (for the validation cohort only: 95.0%; 95% CI = 73.1% to 99.7%). This markedly exceeded corresponding results for cytology (51.7%; 95% CI = 32.9% to 70.1%; P = .003) and CEA (57.1%; 95% CI = 34.4% to 77.4%; P = .02).
  
  
  CONCLUSIONS
  Proteomic cyst fluid mucin profiling robustly discriminates benign, premalignant, and malignant PCLs. Consequently, it may improve pancreatic cancer prevention and reduce the morbidity burden of unwarranted pancreatic surgery.
authors: Affiliations of authors: Department of Medical Biochemistry, University of Gothenburg, Gothenburg, Sweden (KSJ, GCH); Department of Gastroenterology and Hepatology (KSJ, HS, RS) and Department of Surgery (AGH), Sahlgrenska University Hospital, Gothenburg, Sweden; Division of Pathology, Department of Laboratory Medicine, Karolinska Institute, Karolinska University Hospital, Stockholm, Sweden (CV).
authors: Karolina S
authors: KS
authors: Jabbar
authors: Caroline
authors: C
authors: Verbeke
authors: Anders G
authors: AG
authors: Hyltander
authors: Henrik
authors: H
authors: Sjövall
authors: Gunnar C
authors: GC
authors: Hansson
authors: Riadh
authors: R
authors: Sadik
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis* / Q000097:blood; D002272:Carcinoembryonic Antigen / Q000097:blood; D002853:Chromatography, Liquid; D020420:Cyst Fluid / Q000737:chemistry*; D004586:Electrophoresis; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D013058:Mass Spectrometry; D008875:Middle Aged; D009077:Mucins / Q000032:analysis* / Q000235:genetics; D010181:Pancreatic Cyst / Q000378:metabolism* / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000737:chemistry / Q000473:pathology*; D011230:Precancerous Conditions / Q000737:chemistry* / Q000473:pathology; D011237:Predictive Value of Tests
chemical_list: D014408:Biomarkers, Tumor; D002272:Carcinoembryonic Antigen; D009077:Mucins