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Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA.
Dig Dis Sci 2018; 63(9):2351-2361DD

Abstract

BACKGROUND

Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas.

AIMS

To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making.

METHODS

We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing.

RESULTS

There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst.

CONCLUSIONS

In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing.

Authors+Show Affiliations

Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal. sandrarfaias@hotmail.com. Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. sandrarfaias@hotmail.com.Molecular Pathobiology Investigation Center, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.Molecular Pathobiology Investigation Center, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal. Faculty of Medicine, University of Lisbon, Lisbon, Portugal.Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal. Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal.Faculty of Medicine, University of Lisbon, Lisbon, Portugal. Gastroenterology Department, Hospital Beatriz Ângelo, Av. Carlos Teixeira, 3, 2670-000, Loures, Portugal.

Pub Type(s)

Comparative Study
Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29796909

Citation

Faias, Sandra, et al. "Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained By EUS-FNA." Digestive Diseases and Sciences, vol. 63, no. 9, 2018, pp. 2351-2361.
Faias S, Duarte M, Albuquerque C, et al. Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA. Dig Dis Sci. 2018;63(9):2351-2361.
Faias, S., Duarte, M., Albuquerque, C., da Silva, J. P., Fonseca, R., Roque, R., ... Cravo, M. (2018). Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA. Digestive Diseases and Sciences, 63(9), pp. 2351-2361. doi:10.1007/s10620-018-5128-y.
Faias S, et al. Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained By EUS-FNA. Dig Dis Sci. 2018;63(9):2351-2361. PubMed PMID: 29796909.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA. AU - Faias,Sandra, AU - Duarte,Marlene, AU - Albuquerque,Cristina, AU - da Silva,João Pereira, AU - Fonseca,Ricardo, AU - Roque,Ruben, AU - Dias Pereira,Antonio, AU - Chaves,Paula, AU - Cravo,Marília, Y1 - 2018/05/24/ PY - 2018/01/12/received PY - 2018/05/17/accepted PY - 2018/5/26/pubmed PY - 2018/9/19/medline PY - 2018/5/26/entrez KW - CEA KW - DNA KW - EUS-FNA KW - Genetic analysis KW - KRAS or GNAS KW - Pancreatic cystic neoplasm SP - 2351 EP - 2361 JF - Digestive diseases and sciences JO - Dig. Dis. Sci. VL - 63 IS - 9 N2 - BACKGROUND: Pancreatic cysts are common incidental findings with malignant potential, raising diagnostic and treatment dilemmas. AIMS: To determine the added value of KRAS and GNAS mutation analysis on cyst classification and decision making. METHODS: We analyzed 52 frozen samples of pancreatic cystic fluid obtained by EUS-FNA between 2008 and 2014. In addition to cytology and CEA, mutations of GNAS (exons 8 and 9) and KRAS (exons 2 and 3) genes were analyzed using Sanger sequencing. RESULTS: There were 52 patients, 67% females, with a mean age of 59 ± 15 years (29-91). Cysts were classified as mucinous in 21 patients (40%) (14 low-risk, seven malignant) and non-mucinous in 31 patients (60%). After EUS-FNA, 11 patients had surgery, six had chemotherapy or palliation, one had endoscopic drainage, and 34 are on follow-up after a mean of 57 months. KRAS mutation was detected in nine and GNAS in two samples. Patients harboring cysts with KRAS mutations were older (p = 0.01), cysts were more commonly mucinous (p = 0.001) and malignant (p = 0.01). KRAS mutations were present in both low-risk and malignant mucinous lesions. For identifying mucinous lesions, CEA > 192 ng/mL performed better (AUC ROC = 93%), whereas for malignant/high-risk mucinous lesions, EUS imaging had the best accuracy (AUC ROC = 88%). After molecular analysis, a modification in cyst classification occurred in ten patients, but was correct in only two, a pseudocyst re-classified as IPMN and a malignant cyst as a non-mucinous cyst. CONCLUSIONS: In this cohort of patients with pancreatic cysts, KRAS and GNAS mutations had no significant diagnostic benefit in comparison with conventional testing. SN - 1573-2568 UR - https://www.unboundmedicine.com/medline/citation/29796909/Clinical_Impact_of_KRAS_and_GNAS_Analysis_Added_to_CEA_and_Cytology_in_Pancreatic_Cystic_Fluid_Obtained_by_EUS_FNA_ L2 - https://doi.org/10.1007/s10620-018-5128-y DB - PRIME DP - Unbound Medicine ER -