Value of adding GNAS testing to pancreatic cyst fluid KRAS and carcinoembryonic antigen analysis for the diagnosis of intraductal papillary mucinous neoplasms

Dig Endosc. 2017 Jan;29(1):111-117. doi: 10.1111/den.12710. Epub 2016 Oct 4.


Background and aim: Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCL). The present study aimed to investigate the value of GNAS testing when added to KRAS and carcinoembryonic antigen (CEA) testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMN).

Methods: Prospectively collected endoscopic ultrasonography fine-needle aspiration (EUS-FNA) data were analyzed retrospectively for GNAS and KRAS mutations and CEA results. IPMN were histologically confirmed or supported by imaging and EUS-FNA findings (KRAS, CEA, cytology). Performance characteristics of GNAS added to KRAS and CEA for the diagnosis of IPMN were calculated.

Results: The study population consisted of 197 patients with cyst fluid test results. Cysts were histologically classified in 33 patients and by clinical criteria in 164 patients. The IPMN group included 108 patients and the non-IPMN group included 89 patients. GNAS was positive in 51 patients (47.2%) with IPMN. Forty-two of these patients (82.3%) also had a KRAS mutation. Adding GNAS to KRAS increased the diagnostic accuracy from 76.6% to 79.1% (P > 0.05). Adding GNAS to CEA increased the diagnostic accuracy from 66.4% to 80.7 % (P < 0.05), but did not achieve a diagnostic superiority to KRAS testing alone (80.7% vs 76.6%, P > 0.05). The diagnostic accuracy of the triple combination was significantly better than all single tests (P < 0.05).

Conclusion: GNAS mutation is a highly specific test for IPMN. When GNAS testing is added to CEA and KRAS, a significantly greater overall accuracy (86.2%) is achieved.

Keywords: GNAS; KRAS; carcinoembryonic antigen; intraductal papillary mucinous neoplasms; pancreas cyst.

MeSH terms

  • Adenocarcinoma, Mucinous / diagnosis
  • Adenocarcinoma, Mucinous / genetics*
  • Adenocarcinoma, Mucinous / metabolism
  • Adult
  • Aged
  • Aged, 80 and over
  • Biomarkers, Tumor / genetics
  • Biomarkers, Tumor / metabolism
  • Carcinoembryonic Antigen / genetics*
  • Carcinoembryonic Antigen / metabolism
  • Carcinoma, Pancreatic Ductal / diagnosis
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Papillary / diagnosis
  • Carcinoma, Papillary / genetics*
  • Carcinoma, Papillary / metabolism
  • Chromogranins / genetics*
  • Chromogranins / metabolism
  • DNA Mutational Analysis
  • DNA, Neoplasm / genetics
  • Endoscopic Ultrasound-Guided Fine Needle Aspiration / methods
  • Female
  • Follow-Up Studies
  • GTP-Binding Protein alpha Subunits, Gs / genetics*
  • GTP-Binding Protein alpha Subunits, Gs / metabolism
  • Humans
  • Male
  • Middle Aged
  • Mutation*
  • Pancreatic Cyst / diagnosis
  • Pancreatic Cyst / genetics
  • Pancreatic Cyst / metabolism
  • Pancreatic Neoplasms / diagnosis
  • Pancreatic Neoplasms / genetics
  • Pancreatic Neoplasms / metabolism
  • Proto-Oncogene Proteins p21(ras) / genetics*
  • Proto-Oncogene Proteins p21(ras) / metabolism
  • Retrospective Studies
  • Young Adult


  • Biomarkers, Tumor
  • Carcinoembryonic Antigen
  • Chromogranins
  • DNA, Neoplasm
  • KRAS protein, human
  • GNAS protein, human
  • GTP-Binding Protein alpha Subunits, Gs
  • Proto-Oncogene Proteins p21(ras)