The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

Abdurrahman Kadayifci, Mohammad Al-Haddad, Mustafa Atar, John DeWitt, David G. Forcione, Stuart Sherman, Brenna W. Casey, Carlos Fernandez-Del Castillo, C. Schmidt, Martha B. Pitman, William R. Brugge

Research output: Contribution to journalArticle

Abstract

Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100% and 93.2%), but low sensitivity (48.3% and 56.3%) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8%) and AUC (0.84) significantly compared to KRAS (65.3% and 0.74) or CEA (65.8% and 0.74) alone, but only in the clinical cohort (P<0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73% vs. 37%, P=0.001). The negative predictive value of KRAS mutation was 77.6% in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use.

Original languageEnglish (US)
Pages (from-to)E391-E396
JournalEndoscopy International Open
Volume4
Issue number4
DOIs
StatePublished - Apr 1 2016

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Pancreatic Cyst
Mutation
Cyst Fluid
Cysts
Neoplasms
Endosonography
Fine Needle Biopsy
Area Under Curve
Cohort Studies
Retrospective Studies

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Gastroenterology

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The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts. / Kadayifci, Abdurrahman; Al-Haddad, Mohammad; Atar, Mustafa; DeWitt, John; Forcione, David G.; Sherman, Stuart; Casey, Brenna W.; Fernandez-Del Castillo, Carlos; Schmidt, C.; Pitman, Martha B.; Brugge, William R.

In: Endoscopy International Open, Vol. 4, No. 4, 01.04.2016, p. E391-E396.

Research output: Contribution to journalArticle

Kadayifci, A, Al-Haddad, M, Atar, M, DeWitt, J, Forcione, DG, Sherman, S, Casey, BW, Fernandez-Del Castillo, C, Schmidt, C, Pitman, MB & Brugge, WR 2016, 'The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts', Endoscopy International Open, vol. 4, no. 4, pp. E391-E396. https://doi.org/10.1055/s-0042-101755
Kadayifci, Abdurrahman ; Al-Haddad, Mohammad ; Atar, Mustafa ; DeWitt, John ; Forcione, David G. ; Sherman, Stuart ; Casey, Brenna W. ; Fernandez-Del Castillo, Carlos ; Schmidt, C. ; Pitman, Martha B. ; Brugge, William R. / The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts. In: Endoscopy International Open. 2016 ; Vol. 4, No. 4. pp. E391-E396.
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abstract = "Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100{\%} and 93.2{\%}), but low sensitivity (48.3{\%} and 56.3{\%}) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8{\%}) and AUC (0.84) significantly compared to KRAS (65.3{\%} and 0.74) or CEA (65.8{\%} and 0.74) alone, but only in the clinical cohort (P<0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73{\%} vs. 37{\%}, P=0.001). The negative predictive value of KRAS mutation was 77.6{\%} in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use.",
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T1 - The value of KRAS mutation testing with CEA for the diagnosis of pancreatic mucinous cysts

AU - Kadayifci, Abdurrahman

AU - Al-Haddad, Mohammad

AU - Atar, Mustafa

AU - DeWitt, John

AU - Forcione, David G.

AU - Sherman, Stuart

AU - Casey, Brenna W.

AU - Fernandez-Del Castillo, Carlos

AU - Schmidt, C.

AU - Pitman, Martha B.

AU - Brugge, William R.

PY - 2016/4/1

Y1 - 2016/4/1

N2 - Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100% and 93.2%), but low sensitivity (48.3% and 56.3%) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8%) and AUC (0.84) significantly compared to KRAS (65.3% and 0.74) or CEA (65.8% and 0.74) alone, but only in the clinical cohort (P<0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73% vs. 37%, P=0.001). The negative predictive value of KRAS mutation was 77.6% in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use.

AB - Background and aims: Pancreatic cyst fluid (PCF) CEA has been shown to be the most accurate preoperative test for detection of cystic mucinous neoplasms (CMNs). This study aimed to assess the added value of PCF KRAS mutational analysis to CEA for diagnosis of CMNs. Patients and methods: This is a retrospective study of prospectively collected endoscopic ultrasonography (EUS) fine-needle aspiration (FNA) data. KRAS mutation was determined by direct sequencing or equivalent methods. Cysts were classified histologically (surgical cohort) or by clinical (EUS or FNA) findings (clinical cohort). Performance characteristics of KRAS, CEA and their combination for detection of a cystic mucinous neoplasm (CMN) and malignancy were calculated. Results: The study cohort consisted of 943 patients: 147 in the surgical cohort and 796 in the clinical cohort. Overall, KRAS and CEA each had high specificity (100% and 93.2%), but low sensitivity (48.3% and 56.3%) for the diagnosis of a CMN. The positivity of KRAS or CEA increased the diagnostic accuracy (80.8%) and AUC (0.84) significantly compared to KRAS (65.3% and 0.74) or CEA (65.8% and 0.74) alone, but only in the clinical cohort (P<0.0001 for both). KRAS mutation was significantly more frequent in malignant CMNs compared to histologically confirmed non-malignant CMNs (73% vs. 37%, P=0.001). The negative predictive value of KRAS mutation was 77.6% in differentiating non-malignant cysts. Conclusions: The detection of a KRAS mutation in PCF is a highly specific test for mucinous cysts. It outperforms CEA for sensitivity in mucinous cyst diagnosis, but the data does not support its routine use.

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