p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis

Löhr, Matthias; Müller, Petra; Móra, Josefina; Brinkmann, Beate; Ostwald, Christiane; Farré, Antonio López; Lluı́s, Fèlix; Adam, Ulrich; Stubbe, Jens; Plath, Franziska; Nizze, H; Hopt, U. T.; M, Barten; Capellà, Gabriel; Liebe, Stefan

doi:10.1067/mge.2001.112711

Cited by 47 publications

(42 citation statements)

References 54 publications

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“…No mutations in TP53 were detected in patients with low-grade IPMNs. In addition, the authors did not identify TP53 mutations in subjects with chronic pancreatitis, but prior studies using endoscopic retrograde cholangiopancreatography-collected juice have found TP53 mutations in a small percentage of individuals (24)(25)(26). Although TP53 mutations may prove to be a useful marker in determining the presence of high-grade lesions and invasive adenocarcinoma, additional studies are required to assess its accuracy in patients undergoing pancreatic cyst evaluation.…”

Section: Discussionmentioning

confidence: 83%

PreoperativeGNASandKRASTesting in the Diagnosis of Pancreatic Mucinous Cysts

Singhi¹,

Nikiforova²,

Fasanella

et al. 2014

Clinical Cancer Research

174

134

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Purpose: Management guidelines for pancreatic intraductal papillary mucinous neoplasms (IPMN) and mucinous cystic neoplasms (MCN) are based on the assumption that mucinous cysts can be accurately distinguished from other pancreatic cystic lesions. Previous studies using surgical material have identified recurrent mutations in GNAS and KRAS in pancreatic mucinous neoplasms. Yet, the diagnostic utility of testing for both genes in pancreatic cyst fluid obtained by endoscopic ultrasound-fine-needle aspiration (EUS-FNA) remains unclear.Experimental Design: GNAS and KRAS testing was performed on EUS-FNA pancreatic cyst fluid from 91 pancreatic cysts: 41 IPMNs, 9 IPMNs with adenocarcinoma, 16 MCNs, 10 cystic pancreatic neuroendocrine tumors (PanNET), 9 serous cystadenomas (SCA), 3 retention cysts, 2 pseudocysts, and 1 lymphoepithelial cyst.Results: Mutations in GNAS were detected in 16 (39%) IPMNs and 2 (22%) IPMNs with adenocarcinoma. KRAS mutations were identified in 28 (68%) IPMNs, 7 (78%) IPMNs with adenocarcinoma, and 1 (6%) MCN. Mutations in either gene were present in 34 (83%) IPMNs, 8 (89%) IPMNs with adenocarcinoma, and 1 (6%) MCN. No mutations were found in cystic PanNETs, SCAs, retention cysts, pseudocysts, and a lymphoepithelial cyst. GNAS and KRAS mutations had 100% specificity [95% confidence interval (CI), 0.83-1.00] but 65% sensitivity (95% CI, 0.52-0.76) for mucinous differentiation. Among IPMNs, mutations in either gene had 98% specificity (95% CI, 0.86-1.00) and 84% sensitivity (95% CI, 0.70-0.92).Conclusions: The combination of GNAS and KRAS testing was highly specific and sensitive for IPMNs; however, the lack of sensitivity for MCNs highlights the need for additional markers to improve the detection of pancreatic mucinous neoplasms.

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Section: Discussionmentioning

confidence: 83%

PreoperativeGNASandKRASTesting in the Diagnosis of Pancreatic Mucinous Cysts

Singhi¹,

Nikiforova²,

Fasanella

et al. 2014

Clinical Cancer Research

174

134

View full text Add to dashboard Cite

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“…Patients with chronic pancreatitis have an increased risk of pancreatic cancer, estimated at 1.8% at 10 years and 4% at 20 years (Lowenfels et al, 1993). Three studies have evaluated occurrence of pancreatic cancer in patients with chronic pancreatitis with respect to KRAS2 mutations in pancreatic juice: only one found an increase in pancreatic cancer in patients with KRAS2 mutations with methodological limitations (few cases, early diagnosis of cancer after inclusion) (Furuya et al, 1997;Lohr et al, 2001;Queneau et al, 2001). To our knowledge, no study focused on the incidence of pancreatic cancer in patients with chronic pancreatitis according to serum KRAS2 mutations.…”

Section: Molecular and Cellular Pathologymentioning

confidence: 99%

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA

et al. 2002

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KRAS2 mutations in codon 12 have been detected in about 80% of pancreatic cancers. The aim of this study was to evaluate the value of KRAS2 mutations detection in circulating deoxyribo nucleic acid to differentiate pancreatic cancer from chronic pancreatitis. Circulating deoxyribo nucleic acid was isolated from serum in 47 patients with histologically proven pancreatic adenocarcinomas (26 males, median age 65 years) and 31 controls with chronic pancreatitis (26 males, median age 48 years). Mutations at codon 12 of KRAS2 gene were searched for using polymerase chain reaction and allele specific amplification. Serum carbohydrate antigen 19.9 levels were also determined. KRAS2 mutations were found in 22 patients (47%) with pancreatic cancer and in four controls with chronic pancreatitis (13%) (P50.002). None of the latter developed a pancreatic cancer within the 36 months of median follow-up. The sensitivity, specificity, positive and negative predictive values of serum serum KRAS2 mutations for the diagnosis of pancreatic cancer were 47, 87, 85 and 52%, respectively. KRAS2 mutations were not related to age, gender, smoking habit, tumour stage, or survival. Among the 26 patients with normal or non-contributive (due to cholestasis) serum carbohydrate antigen 19.9 levels, 14 (54%) had KRAS2 mutations. The combination of KRAS2 and carbohydrate antigen 19.9 gave a sensitivity, specificity, positive and negative predictive values for the diagnosis of pancreatic cancer of 98, 77, 87 and 96%, respectively. Detection of KRAS2 mutations in circulating deoxyribo nucleic acid has a low sensitivity but a specificity about 90% for the diagnosis of pancreatic cancer. It seems particularly useful when serum carbohydrate antigen 19.9 levels are normal or inconclusive. A combined normal serum carbohydrate antigen 19.9 and absence of circulating KRAS2 mutations makes the diagnosis of pancreatic cancer extremely unlikely.

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“…In addition, patients with chronic pancreatitis constitute a high-risk group for ordinary-type pancreatic cancer [73][74][75]. Although clear evidence for testing is lacking, many patients with chronic pancreatitis lead a lifestyle associated with carcinogenic risks (alcohol drinking and/or smoking), and it is useful to perform cancer screening [65,[76][77][78][79][80][81].…”

Section: Pain Managementmentioning

confidence: 99%

Evidence-based clinical practice guidelines for chronic pancreatitis 2015

et al. 2016

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Chronic pancreatitis is considered to be an irreversible progressive chronic inflammatory disease. The etiology and pathology of chronic pancreatitis are complex; therefore, it is important to correctly understand the stage and pathology and provide appropriate treatment accordingly. The newly revised Clinical Practice Guidelines of Chronic Pancreatitis 2015 consist of four chapters, i.e., diagnosis, staging, treatment, and prognosis, and includes a total of 65 clinical questions. These guidelines have aimed at providing certain directions and clinically practical contents for the management of chronic pancreatitis, preferentially adopting clinically useful articles. These revised guidelines also refer to early chronic pancreatitis based on the Criteria for the Diagnosis of Chronic Pancreatitis 2009. They include such items as health insurance coverage of high-titer lipase preparations and extracorporeal shock wave lithotripsy, new antidiabetic drugs, and the definition of and treatment approach to pancreatic pseudocyst. The accuracy of these guidelines has been improved by examining and adopting new evidence obtained after the publication of the first edition.

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p53 and K-ras mutations in pancreatic juice samples from patients with chronic pancreatitis

Cited by 47 publications

References 54 publications

PreoperativeGNASandKRASTesting in the Diagnosis of Pancreatic Mucinous Cysts

PreoperativeGNASandKRASTesting in the Diagnosis of Pancreatic Mucinous Cysts

Differential diagnosis between chronic pancreatitis and pancreatic cancer: value of the detection of KRAS2 mutations in circulating DNA

Evidence-based clinical practice guidelines for chronic pancreatitis 2015

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