KRAS mutation assay on EUS-FNA specimens from pacients with pancreatic mass
Authors:
MUDr. Bohuš Bunganič 1; Mgr. Tereza Hálková; RNDr. Ph.D. Lucie Benešová; Bc. Barbora Belšánová; MUDr. Martin Laclav; MUDr. Martina Hrůzová; MUDr. Eva Traboulsi; prof. MUDr. CSc. Přemysl Frič; MUDr. Ph.D. Štěpán Suchánek; RNDr. Ph.D. Marek Minárik; prof. MUDr. Ph.D. Miroslav Zavoral
Authors place of work:
Interní klinika 1. LF UK a ÚVN − Vojenské fakultní nemocnice Praha: U Vojenské nemocnice 1200, 160 00 Praha
1; Centrum aplikované genomiky solidních nádorů (CEGES), Genomac výzkumný ústav, s. r. o., Praha: Drnovská 1112/60, 161 00 Praha
6
Published in the journal:
Čas. Lék. čes. 2016; 155: 48-51
Category:
Original Article
Summary
Differential diagnosis of solid pancreatic masses using EUS FNA is in 10−15 % of cases still challenging. Promising method, which helps to distinguish between chronic pancreatitis and cancer, is point mutations of the proto-oncogene KRAS test. This method is not established in routine clinical practice yet.
Objectives were the determination of the sensitivity of the KRAS assay using various kinds of samples of patients with pancreatic mass and testing the effect of the presence of KRAS mutations on the prognosis of survival. 147 patients underwent EUS-FNA examination of pancreatic mass, accompanied by blood sampling with subsequent separation of plasma for the detection of circulating tumor DNA. Part of biopsy sample was left native in a stabilizing solution and part as cytological smear. Samples (native aspirates, cytological smears, plasma) were examined for the presence of KRAS mutation by heteroduplex analysis, denaturing capillary electrophoresis.
Among 147 patients with pancreatic masses, 118 were diagnosed as a cancer, 26 chronic pancreatitis, 3 neuroendocrine tumor. In total 147 native aspirates, 118 cytological smears and 94 plasma samples were examined. The highest sensitivity of KRAS mutation was reached in the group of pancreatic cancer patients using cytology, in which 90 % of KRAS mutation was detected (106/118 of the samples). When using the native cellular aspirates, mutation was detected in 78 % (92/118 samples), and examination of plasma was positive in 27 % (24/90 samples). In four patients with chronic pancreatitis KRAS mutations was detected, although none has been cytologically confirmed as a cancer. Two of these four patients were confirmed in the course of the disease as a cancer, one patient died because of alcoholic delirium and the last one was indicated for surgery recently.
Examination of KRAS mutations can be performed in all patients undergoing EUS-FNA, with the cytology being the most reliable type of sample for genetic tests. KRAS examination would be reasonable to introduce into routine clinical practice in a group of patients with unclear differential diagnosis of chronic pancreatitis, especially in those with suspicion of cancer in inflammatory terrain.
Kexwords:
pancreatic cancer, chronic pancreatitis, KRAS mutation , EUS-FNA
Zdroje
1. Müller MF, Meyenberger C, Bertschinger P et al. Pancreatic tumors: evaluation with endoscopic US, CT, and MR imaging. Radiology 1994; 190(3): 745–751.
2. Rosewicz S, Wiedenmann B. Pancreatic carcinoma. Lancet 1997 Feb 15; 349(9050): 485–489.
3. Varadarajulu S, Tamhane A, Eloubeidi MA. Yield of EUS-guided FNA of pancreatic masses in the presence or the absence of chronic pancreatitis. Gastrointest Endosc 2005 Nov; 62(5): 728–736.
4. Pietryga JA, Morgan DE. Imaging preoperatively for pancreatic adenocarcinoma. J Gastrointest Oncol 2015 Aug; 6(4): 343–357.
5. Hanada K, Okazaki A, Hirano N et al. Diagnostic strategies for early pancreatic cancer. J Gastroenterol 2015 Feb; 50(2): 147–154.
6. Hanada K, Okazaki A, Hirano N et al. Effective screening for early diagnosis of pancreatic cancer. Best Pract Res Clin Gastroenterol 2015; 29(6): 929–939.
7. Chari ST, Kelly K, Hollingsworth MA et al. Early detection of sporadic pancreatic cancer: summative review. Pancreas 2015 Jul; 44(5): 693–712.
8. Kenner BJ, Chari ST, Cleeter DF, Go VL. Early detection of sporadic pancreatic cancer: strategic map for innovation––a white paper. Pancreas 2015 Jul; 44(5): 686–692.
9. Hruban RH, Goggins M, Parsons J, Kern SE. Progression model for pancreatic cancer. Clin Cancer Res 2000 Aug; 6(8): 2969–2972.
10. Biankin AV, Waddell N, Kassahn KS et al. Pancreatic cancer genomes reveal aberrations in axon guidance pathway genes. Nature 2012 Nov 15; 491(7424): 399–405.
11. Ginestà MM, Mora J, Mayor R et al. Genetic and epigenetic markers in the evaluation of pancreatic masses. J Clin Pathol 2013 Mar; 66(3): 192–197.
12. Majumder S, Chari ST, Ahlquist DA. Molecular detection of pancreatic neoplasia: current status and future promise. World J Gastroenterol 2015 Oct 28; 21(40): 11387–11395.
13. Kitano M, Kudo M, Yamao K et al. Characterization of small solid tumors in the pancreas: the value of contrast-enhanced harmonic endoscopicultrasonography. Am J Gastroenterol 2012 Feb; 107(2): 303–310.
14. Catalano MF, Sahai A, Levy M et al. EUS-based criteria for the diagnosis of chronic pancreatitis: the Rosemont classification. Gastrointest Endosc 2009 Jun; 69(7): 1251–1261.
15. Šálek C, Benešová L, Zavoral M et al. Evaluation of clinical relevance of examining K-ras, p16 and p53 mutations along with allelic losses at 9p and 18q in EUS-guided fine needle aspiration samples of patients with chronic pancreatitis and pancreatic cancer. World J Gastroenterol 2007 Jul 21; 13(27): 3714–3720.
16. Šálek C, Minaříková P, Benešová L et al. Mutation status of K-ras, p53 and allelic losses at 9p and 18q are not prognostic markers in patients with pancreatic cancer. Anticancer Res 2009 May; 29(5): 1803–1810.
17. Tada M, Komatsu Y, Kawabe T et al. Quantitative analysis of K-ras gene mutation in pancreatic tissue obtained by endoscopic ultrasonography-guided fine needle aspiration: clinical utility for diagnosis of pancreatic tumor. Am J Gastroenterol 2002 Sep; 97(9): 2263–2270.
18. Takahashi K, Yamao K, Okubo K et al. Differential diagnosis of pancreatic cancer and focal pancreatitis by using EUS-guided FNA. Gastrointest Endosc 2005 Jan; 61(1): 76–79.
19. Ginestà MM, Mora J, Mayor R et al. Genetic and epigenetic markers in the evaluation of pancreatic masses. J Clin Pathol 2013 Mar; 66(3): 192–197.
20. Khalid A, Dewitt J, Ohori NP et al. EUS-FNA mutational analysis in differentiating autoimmune pancreatitis and pancreatic cancer. Pancreatology 2011; 11(5): 482–486.
21. Bournet B, Gayral M, Torrisani J et al. Role of endoscopic ultrasound in the molecular diagnosis of pancreatic cancer. World J Gastroenterol 2014 Aug 21; 20(31): 10758–10768.
22. Rachakonda PS, Bauer AS, Xie H et al. Somatic mutations in exocrine pancreatic tumors: association with patient survival. PLoS One 2013; 8(4): e60870.
23. Pellisé M, Castells A, Ginès A et al. Clinical usefulness of KRAS mutational analysis in the diagnosis of pancreatic adenocarcinoma by means of endosonography-guided fine-needle aspiration biopsy. Aliment Pharmacol Ther 2003 May 15; 17(10): 1299–1307.
24. Zheng M, Liu LX, Zhu AL et al. K-ras gene mutation in the diagnosis of ultrasound guided fine-needle biopsy of pancreatic masses. World J Gastroenterol 2003 Jan; 9(1): 188–191.
25. Maluf-Filho F, Kumar A, Gerhardt R et al. Kras mutation analysis of fine needle aspirate under EUS guidance facilitates risk stratification of patients with pancreatic mass. J Clin Gastroenterol 2007 Nov-Dec; 41(10): 906–910.
26. Bournet B, Souque A, Senesse P et al. Endoscopic ultrasound-guided fine-needle aspiration biopsy coupled with KRAS mutation assay to distinguish pancreatic cancer from pseudotumoral chronic pancreatitis. Endoscopy 2009 Jun; 41(6): 552–557.
Štítky
Addictology Allergology and clinical immunology Angiology Audiology Clinical biochemistry Dermatology & STDs Paediatric gastroenterology Paediatric surgery Paediatric cardiology Paediatric neurology Paediatric ENT Paediatric psychiatry Paediatric rheumatology Diabetology Pharmacy Vascular surgery Pain management Dental HygienistČlánok vyšiel v časopise
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