title: Fluorescence in situ hybridization and K-ras analyses improve diagnostic yield of endoscopic ultrasound-guided fine-needle aspiration of solid pancreatic masses.
abstract: OBJECTIVE
  Endoscopic ultrasound (EUS)-guided fine-needle aspiration (FNA) is the main diagnostic modality for pancreatic mass lesions. However, cytology is often indeterminate, leading to repeat FNAs and delay in care. Here, we evaluate whether combining routine cytology with fluorescence in situ hybridization (FISH) and K-ras/p53 analyses improves diagnostic yield of pancreatic EUS-FNA.
  
  
  METHODS
  Fifty EUS-FNAs of pancreatic masses in 46 patients were retrospectively analyzed. Mean follow-up was 68 months. Thirteen initial cytologic samples (26%) were benign, 23 malignant (46%), and 14 atypical (28%). We performed FISH for p16, p53, LPL, c-Myc, MALT1, topoisomerase 2/human epidermal growth factor receptor 2, and EGFR, as well as K-ras/p53 mutational analyses.
  
  
  RESULTS
  On final diagnosis, 11 (79%) of atypical FNAs were malignant, and 3 benign (21%). Fluorescence in situ hybridization was negative in all benign and all atypical samples with final benign diagnosis. Fluorescence in situ hybridization plus K-ras analysis correctly identified 60% of atypical FNAs with final malignant diagnosis. Combination of routine cytology with positive FISH and K-ras analyses yielded 87.9% sensitivity, 93.8% specificity, 96.7% positive predictive value, 78.9% negative predictive value, and 89.8% accuracy.
  
  
  CONCLUSIONS
  Combining routine cytology with FISH and K-ras analyses improves diagnostic yield of EUS-FNA of solid pancreatic masses. We propose to include these ancillary tests in the workup of atypical cytology from pancreatic EUS-FNA.
authors.affiliation: Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance, CA 90502, USA. sreicher@sbcglobal.net
authors.forename: Sofiya
authors.initials: S
authors.lastname: Reicher
authors.forename: Fatih Z
authors.initials: FZ
authors.lastname: Boyar
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Vladimira
authors.initials: V
authors.lastname: Sulcova
authors.forename: Sally
authors.initials: S
authors.lastname: Agersborg
authors.forename: Visal
authors.initials: V
authors.lastname: Nga
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhou
authors.forename: Gang
authors.initials: G
authors.lastname: Li
authors.forename: Rose
authors.initials: R
authors.lastname: Venegas
authors.forename: Samuel W
authors.initials: SW
authors.lastname: French
authors.forename: David S
authors.initials: DS
authors.lastname: Chung
authors.forename: Bruce E
authors.initials: BE
authors.lastname: Stabile
authors.forename: Viktor E
authors.initials: VE
authors.lastname: Eysselein
authors.forename: Arturo
authors.initials: A
authors.lastname: Anguiano
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000235:genetics*; D044963:Biopsy, Fine-Needle; D002140:California; D016009:Chi-Square Distribution; D004252:DNA Mutational Analysis; D019160:Endosonography; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010182:Pancreatic Diseases / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012189:Retrospective Studies; D012680:Sensitivity and Specificity; D013997:Time Factors; D016159:Tumor Suppressor Protein p53 / Q000235:genetics; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins