Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts

Aatur D. Singhi, Marina N. Nikiforova, Kenneth E. Fasanella, Kevin M. McGrath, Reetesh K. Pai, N. Paul Ohori, Tanner L. Bartholow, Randall E. Brand, Jennifer S. Chennat, Xuong Lu, Georgios I. Papachristou, Adam Slivka, Herbert J. Zeh, Amer H. Zureikat, Kenneth K. Lee, Allan Tsung, Geeta S. Mantha, Asif Khalid

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Abstract

Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.

Original languageEnglish (US)
Pages (from-to)4381-4389
Number of pages9
JournalClinical Cancer Research
Volume20
Issue number16
DOIs
StatePublished - Aug 15 2014
Externally publishedYes

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Pancreatic Cyst
Cysts
Mutation
Adenocarcinoma
Confidence Intervals
Cyst Fluid
Fine Needle Biopsy
Pancreatic Neoplasms
Neoplasms
Serous Cystadenoma
Genes
Neuroendocrine Tumors
Research Design
Guidelines

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Singhi, A. D., Nikiforova, M. N., Fasanella, K. E., McGrath, K. M., Pai, R. K., Ohori, N. P., ... Khalid, A. (2014). Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. Clinical Cancer Research, 20(16), 4381-4389. https://doi.org/10.1158/1078-0432.CCR-14-0513

Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. / Singhi, Aatur D.; Nikiforova, Marina N.; Fasanella, Kenneth E.; McGrath, Kevin M.; Pai, Reetesh K.; Ohori, N. Paul; Bartholow, Tanner L.; Brand, Randall E.; Chennat, Jennifer S.; Lu, Xuong; Papachristou, Georgios I.; Slivka, Adam; Zeh, Herbert J.; Zureikat, Amer H.; Lee, Kenneth K.; Tsung, Allan; Mantha, Geeta S.; Khalid, Asif.

In: Clinical Cancer Research, Vol. 20, No. 16, 15.08.2014, p. 4381-4389.

Research output: Contribution to journalArticle

Singhi, AD, Nikiforova, MN, Fasanella, KE, McGrath, KM, Pai, RK, Ohori, NP, Bartholow, TL, Brand, RE, Chennat, JS, Lu, X, Papachristou, GI, Slivka, A, Zeh, HJ, Zureikat, AH, Lee, KK, Tsung, A, Mantha, GS & Khalid, A 2014, 'Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts', Clinical Cancer Research, vol. 20, no. 16, pp. 4381-4389. https://doi.org/10.1158/1078-0432.CCR-14-0513
Singhi AD, Nikiforova MN, Fasanella KE, McGrath KM, Pai RK, Ohori NP et al. Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. Clinical Cancer Research. 2014 Aug 15;20(16):4381-4389. https://doi.org/10.1158/1078-0432.CCR-14-0513
Singhi, Aatur D. ; Nikiforova, Marina N. ; Fasanella, Kenneth E. ; McGrath, Kevin M. ; Pai, Reetesh K. ; Ohori, N. Paul ; Bartholow, Tanner L. ; Brand, Randall E. ; Chennat, Jennifer S. ; Lu, Xuong ; Papachristou, Georgios I. ; Slivka, Adam ; Zeh, Herbert J. ; Zureikat, Amer H. ; Lee, Kenneth K. ; Tsung, Allan ; Mantha, Geeta S. ; Khalid, Asif. / Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts. In: Clinical Cancer Research. 2014 ; Vol. 20, No. 16. pp. 4381-4389.
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abstract = "Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39{\%}) IPMNs and 2 (22{\%}) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68{\%}) IPMNs, 7 (78{\%}) IPMNs with adenocarcinoma, and 1 (6{\%}) MCN. Mutations in either gene were present in 34 (83{\%}) IPMNs, 8 (89{\%}) IPMNs with adenocarcinoma, and 1 (6{\%}) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100{\%} specificity [95{\%} confidence interval (CI), 0.83-1.00] but 65{\%} sensitivity (95{\%} CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98{\%} specificity (95{\%} CI, 0.86-1.00) and 84{\%} sensitivity (95{\%} CI, 0.70-0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.",
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T1 - Preoperative GNAS and KRAS testing in the diagnosis of pancreatic mucinous cysts

AU - Singhi, Aatur D.

AU - Nikiforova, Marina N.

AU - Fasanella, Kenneth E.

AU - McGrath, Kevin M.

AU - Pai, Reetesh K.

AU - Ohori, N. Paul

AU - Bartholow, Tanner L.

AU - Brand, Randall E.

AU - Chennat, Jennifer S.

AU - Lu, Xuong

AU - Papachristou, Georgios I.

AU - Slivka, Adam

AU - Zeh, Herbert J.

AU - Zureikat, Amer H.

AU - Lee, Kenneth K.

AU - Tsung, Allan

AU - Mantha, Geeta S.

AU - Khalid, Asif

PY - 2014/8/15

Y1 - 2014/8/15

N2 - Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.

AB - Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear. Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst. Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92). Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.

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