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Clinical Impact of KRAS and GNAS Analysis Added to CEA and Cytology in Pancreatic Cystic Fluid Obtained by EUS-FNA

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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.

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Acknowledgments

We would like to thank Susan Marum, MD for the English language review of this manuscript.

Funding

The current study was supported by a Research Grant from Clube Português do Pâncreas, Bolsa, 2015, that had no role in any stage of the study, from design to submission for publication.

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Authors and Affiliations

  1. Gastroenterology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal

    Sandra Faias, João Pereira da Silva & Antonio Dias Pereira

  2. Faculty of Health Sciences, University of Beira Interior, Covilhã, Portugal

    Sandra Faias & Paula Chaves

  3. Molecular Pathobiology Investigation Center, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal

    Marlene Duarte & Cristina Albuquerque

  4. Pathology Department, Instituto Português de Oncologia de Lisboa Francisco Gentil EPE, Rua Prof Lima Basto, 1099-023, Lisbon, Portugal

    Ricardo Fonseca, Ruben Roque & Paula Chaves

  5. Faculty of Medicine, University of Lisbon, Lisbon, Portugal

    Ricardo Fonseca & Marília Cravo

  6. Gastroenterology Department, Hospital Beatriz Ângelo, Av. Carlos Teixeira, 3, 2670-000, Loures, Portugal

    Marília Cravo

Authors
  1. Sandra Faias
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  2. Marlene Duarte
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Correspondence to Sandra Faias.

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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 63, 2351–2361 (2018). https://doi.org/10.1007/s10620-018-5128-y

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  • DOI: https://doi.org/10.1007/s10620-018-5128-y

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