title: Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with a KRAS mutation assay using allelic discrimination improves the diagnosis of pancreatic cancer.
abstract: OBJECTIVE
  Mutation of the KRAS oncogene is present in 75% to 95% of pancreatic cancer tissues. This study aimed to evaluate whether endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA), combined with analysis of the KRAS mutation, improves the diagnosis of pancreatic cancer in cases of inconclusive or doubtful cytopathologic analysis.
  
  
  METHODS
  We prospectively included 186 patients with a pancreatic mass (103 men; mean age: 62 y). Cytopathology and KRAS mutations, using TaqMan MGB allelic discrimination, were performed on EUS-FNA material. A final diagnosis was obtained from EUS-FNA analysis and/or a subsequent biopsy if necessary, and/or surgery, and follow-up: these were pancreatic adenocarcinoma (n=104), other malignant pancreatic tumors (n=22), and benign lesions (n=60, including 35 cases of chronic pancreatitis).
  
  
  RESULTS
  Inconclusive or doubtful (low-grade dysplasia or atypia) cytopathology was found in 68 cases. Of these, 29 patients who had adenocarcinoma were subsequently diagnosed, including 19 cases with a former KRAS mutation. Sensitivity, specificity, positive and negative predictive values, and overall accuracy of cytopathology alone to diagnose adenocarcinoma were 73%, 100%, 100%, 75%, and 85%, respectively. When KRAS mutation analysis was combined with pathology, these values reached 88%, 99%, 99%, 89%, and 93%, respectively. The performance of EUS-FNA to diagnose malignancy was similarly improved after the KRAS-mutation assay (negative predictive value increased from 67% to 88%; accuracy increased from 85% to 94%).
  
  
  CONCLUSIONS
  EUS-FNA plus KRAS-mutation analysis, using allelic discrimination, is accurate and improves the diagnosis of pancreatic adenocarcinoma when pathology is inconclusive or doubtful.
authors.affiliation: *Department of Gastroenterology †INSERM UMR 1037, CHU Toulouse Rangueil ‡Department of Pathology, CHU Toulouse Purpan, University of Toulouse, Toulouse, France.
authors.forename: Barbara
authors.initials: B
authors.lastname: Bournet
authors.forename: Janick
authors.initials: J
authors.lastname: Selves
authors.forename: David
authors.initials: D
authors.lastname: Grand
authors.forename: Marie
authors.initials: M
authors.lastname: Danjoux
authors.forename: Naima
authors.initials: N
authors.lastname: Hanoun
authors.forename: Pierre
authors.initials: P
authors.lastname: Cordelier
authors.forename: Louis
authors.initials: L
authors.lastname: Buscail
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000473:pathology*; D004252:DNA Mutational Analysis / Q000379:methods; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology*; D050500:Pancreatitis, Chronic / Q000235:genetics / Q000473:pathology; D011237:Predictive Value of Tests; D011446:Prospective Studies; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins