The Value of Adding GNAS Testing to Pancreatic Cyst Fluid KRAS and CEA Analysis for the Diagnosis of Intraductal Papillary Mucinous Neoplasms

Objectives

Molecular analysis of pancreatic cyst fluid (PCF) has been proposed as a novel method for differentiating pancreatic cystic lesions (PCLs). This study aimed to investigate the value of GNAS testing when added to KRAS and CEA testing of PCF for the diagnosis of intraductal papillary mucinous neoplasms (IPMNs).

Methods

Prospectively collected endoscopic ultrasonography-fine needle aspiration (EUS-FNA) data was analyzed retrospectively for GNAS, KRAS mutations and CEA results. IPMNs 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 IPMNs 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. GNAS mutation was detected in one pseudocyst case. 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.

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