KRAS mutation analysis by next-generation sequencing in endoscopic ultrasound-guided sampling for solid liver masses.
OBJECTIVE
KRAS mutation analysis may provide ancillary diagnostic yield in an endoscopic ultrasound (EUS)-guided histopathological evaluation. We evaluated the clinical impact of KRAS mutation analysis with cytological and histological evaluations in EUS-guided tissue sampling, using a core biopsy needle for solid liver masses.


METHODS
EUS-guided fine needle biopsy (EUS-FNB) using a core biopsy needle was performed in patients with primary or metastatic liver masses that were suspected malignancies. KRAS mutations were analyzed in all specimens obtained. The peptide nucleic acid (PNA)-mediated polymerase chain reaction (PCR) clamping method was compared with a next-generation sequencing (NGS) method for detecting KRAS mutations.


RESULTS
EUS-FNB with a core biopsy needle was performed in 28 patients with solid liver masses located in the liver's left lobe. The diagnostic accuracies for malignancy of on-site cytology, cytology using Papanicolaou staining, and histology including immunohistochemical stains were 82.1%, 85.7%, and 89.3%, respectively. KRAS gene mutations were observed in 14.3% of patients by the PNA-PCR clamping method. The NGS method detected more KRAS mutations than the PNA-PCR clamping method: in 25% of patients. Adding the results of KRAS mutation analysis to the cytohistopathological evaluation, the overall diagnostic accuracy of EUS-guided tissue sampling was 96.4%.


CONCLUSIONS
EUS-guided tissue sampling for solid liver masses in the left lobe provided high diagnostic accuracy from cytological and histological evaluations. KRAS mutation analysis provided additional diagnostic yield in patients with inconclusive cytohistopathological results from EUS-guided tissue sampling. The NGS method detected additional KRAS mutations in patients with negative PNA-mediated PCR clamping test results.
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Hyun Jong
HJ
Choi
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Jong Ho
JH
Moon
Department of Pathology, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Hee Kyung
HK
Kim
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Yun Nah
YN
Lee
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Tae Hoon
TH
Lee
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Sang-Woo
SW
Cha
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Young Deok
YD
Cho
Digestive Disease Center and Research Institute, Department of Internal Medicine, SoonChunHyang University School of Medicine, Bucheon and Seoul, Korea.
Sang-Heum
SH
Park
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D004252:DNA Mutational Analysis / Q000379:methods*; D061765:Endoscopic Ultrasound-Guided Fine Needle Aspiration; D005260:Female; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009154:Mutation; D016133:Polymerase Chain Reaction / Q000379:methods*; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics*; D013048:Specimen Handling / Q000379:methods*
C117307:KRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)
KRAS mutation; endoscopic ultrasonography; fine needle biopsy; solid liver mass