Kras mutation analysis of fine needle aspirate under EUS guidance facilitates risk stratification of patients with pancreatic mass.
OBJECTIVE
The accuracy of endoscopic ultrasound-fine needle aspiration cytology (EUS-FNAC) for the diagnosis of pancreatic cancer is suboptimal. Mutational activation of the kras oncogene is almost universally present in pancreatic cancer tissue. We, therefore, investigated if analysis for mutant kras gene in the EUS-FNAC aspirates supplements cytopathology for the diagnosis of pancreatic adenocarcinoma (PAC).


METHODS
EUS-FNAC specimens obtained from 74 patients with pancreatic masses were analyzed for the presence of kras mutation on codon 12 using polymerase chain reaction-restriction fragment length polymorphism and MvaI restriction enzyme. Definitive diagnosis was based on surgical pathology or long-term follow-up (median 27.8 mo); 57 patients had PAC, 11 patient's chronic pancreatitis, and 9 patient's nonfunctioning neuroendocrine tumors.


RESULTS
Analysis of mutant kras gene in addition to cytopathology allowed the detection of PAC in 4 additional patients as compared with cytopathology alone. Cytopathology and kras mutant analysis were negative for PAC in 17 patients of whom 6 patients (35%) had PAC. The respective sensitivity (90.9% vs. 82.5%), specificity (47.6% vs. 97.9%), positive predictive value (89.5% vs. 83.8%), negative predictive value (98.1% vs. 94.1%), accuracy (89.2% vs. 58.8%) of cytopathology plus kras mutation versus cytopathology were numerically superior but did not reach statistical significance.


CONCLUSIONS
Analysis for the presence of mutant kras gene supplements conventional cytopathology for the diagnosis of PAC even without a cytopathologist in attendance and using only 3 needle passes. Among patients with negative cytopathology, the presence of kras mutation represents pancreatic cancer while the absence of kras mutation increases the possibility of benign lesion.
Maluf-Filho
Fauze
F
Gastrointestinal Endoscopy Division, University of São Paulo School of Medicine, São Paulo, Brazil.
Kumar
Atul
A
Gerhardt
René
R
Kubrusly
Márcia
M
Sakai
Paulo
P
Hondo
Fabio
F
Matuguma
Sergio Eiji
SE
Artifon
Everson
E
Monteiro da Cunha
José Eduardo
JE
César Machado
Marcel Cerqueira
MC
Ishioka
Shinichi
S
Forero
Elias
E
D000230:Adenocarcinoma / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D000328:Adult; D000368:Aged; D044963:Biopsy, Fine-Needle; D003581:Cytodiagnosis; D019160:Endosonography / Q000379:methods*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D010179:Pancreas / Q000473:pathology*; D010190:Pancreatic Neoplasms / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D011237:Predictive Value of Tests; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012680:Sensitivity and Specificity; D018631:ras Proteins / Q000235:genetics*
C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins