K-ras mutation analysis of residual liquid-based cytology specimens from endoscopic ultrasound-guided fine needle aspiration improves cell block diagnosis of pancreatic ductal adenocarcinoma

• Published in: PloS one Vol. 13; no. 3; p. e0193692
• Main Authors: Sekita-Hatakeyama, Yoko, Nishikawa, Takeshi, Takeuchi, Mao, Morita, Kouhei, Takeda, Maiko, Hatakeyama, Kinta, Nakai, Tokiko, Uchiyama, Tomoko, Itami, Hiroe, Fujii, Tomomi, Mitoro, Akira, Sho, Masayuki, Ohbayashi, Chiho
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 01.03.2018; Public Library of Science (PLoS)
• Subjects: Adenocarcinoma; Biology and Life Sciences; Diagnosis; Gene mutation; Genetic aspects; Medicine and Health Sciences; Needle biopsy; Pancreatic cancer; Research and Analysis Methods; Japan
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0193692

Endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) technology is widely used for the diagnosis of pancreatic masses. However, in some cases, inadequate tissue volume or difficulty of morphological diagnosis are constraining factors for adequate cytopathological evaluation. K-ras mutation is the most frequently acquired genetic abnormality, occurring in approximately 90% of all patients with pancreatic ductal adenocarcinoma (PDAC). In the present study, the clinical utility of residual liquid-based cytology (LBC) specimens obtained using EUS-FNA for K-ras mutation analysis was evaluated. In this study, 81 patients with pancreatic lesions were examined. The cell block (CB) specimens separated from EUS-FNA samples were morphologically evaluated by hematoxylin-eosin (HE) staining. Final diagnoses were confirmed by CB specimens, surgical resection specimens, diagnostic imaging, and clinical follow-up. Genomic DNA of residual LBC specimens stored at 4°C for several months were extracted and assessed for K-ras mutations using a fluorescence resonance energy transfer-based preferential homoduplex formation assay. K-ras mutation analysis using residual LBC samples was successful in all cases. The sensitivity, specificity, and accuracy of CB examination alone were 77.4%, 100%, and 81.3%, respectively, and those of the combination of CB examination and K-ras mutation analysis were 90.3%, 92.3%, and 90.7%, respectively. Furthermore, K-ras mutations were detected in 8 (57.1%) of 14 PDAC samples for which the CB results were inconclusive. These findings suggest that K-ras mutation analysis using residual LBC specimens improves the diagnostic accuracy of EUS-FNA.