Usefulness of K-ras gene mutation at codon 12 in bile for diagnosing biliary strictures.

Ito, Reiko; Tamura, Kazuo; Ashida, Hiroshi; Nishiwaki, Manabu; Nishioka, Akihiko; Yamamoto, Yoshihiro; Furuyama, Jun-ichi; Utsunomiya, Joji

doi:10.3892/ijo.12.5.1019

Cited by 9 publications

(13 citation statements)

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“…The frequency of k‐ras mutations in patients with hepatobiliary malignancies has been found to be variable, depending on the kind of tumour. Most of the results were based on tissue; few investigations have included bile samples into the molecular analysis [18,31–33]. The feasibility of utilizing routine plain bile samples procured during ERCP or PTC has not been elucidated before in a large series of patients.…”

Section: Discussionmentioning

confidence: 99%

“…There are very few data on the sensitivity and specificity of molecular analyses in comparison with conventional cytology for ras and none for p53. The reported sensitivities range between 25 and 42% for ras PCR in comparison with 36–59% for cytology; specificity was reported to be 98–100% for both methods [18,31,33,50]. The combination of both techniques only marginally increased the sensitivity.…”

Section: Discussionmentioning

confidence: 99%

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Low frequency of p53 and ras mutations in bile of patients with hepato‐biliary disease: a prospective study in more than 100 patients

Müller

Ostwald

Püschel

et al. 2001

Eur J Clin Investigation

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The diagnosis of biliary disease, namely malignant disorders, is frequently hampered by the inconclusive cytology. We investigated prospectively the frequency of molecular changes in p53 and ras compared with cytology in patients with primary or secondary hepato-biliary disease. We investigated 118 consecutive patients, aged 24-89 with the following clinical diagnoses: choledocho/cholecystolithiasis (28), cholangiocellular carcinoma (21), gall bladder tumor (8), liver metastasis (3), autoimmune disease (8), chronic pancreatitis (16), pancreatic carcinoma (11), papillary disease (4), hepatic cirrhosis (6), cholangitis (2), anomalies (2), and normal (9). Bile was aspirated during routine endoscopic retrograde cholangio pancreatography (ERCP) or percutaneous transhepatic cholangiography (PTC). DNA was prepared freshly from a native aliquot. p53 mutations were detected by polymerase chain reaction (PCR) for exons 5 through 8 followed by TGGE. PCR for ras mutations was performed as RFLP-PCR with sequencing. In four cases, mutations in p53 could be found in exons 6 and 7. Twenty-two samples showed ras mutations; ras mutations were found in choledocholithiasis (4/28), bile duct (5/21), gall bladder (3/8) and pancreatic (1/11) carcinoma, liver metastasis (3/3), ulcerative colitis (2/3), PSC (1/2), and chronic pancreatitis (1/16). Cytology was clearly positive in seven cases, suspicious in three other, inconclusive in six, and negative in the rest. The molecular analysis resulted in a sensitivity of 33% and specificity of 87%, respectively, for the diagnosis of a malignant condition. PCR for p53 and ras mutations may aid the diagnosis of primary and secondary (metastatic) hepatobiliary disease if a malignant condition of the bile ducts and the liver is suspected and cytology is inconclusive or negative. However, the incidence of p53 and ras mutations in bile seems less frequent than in other malignant conditions of the gastrointestinal tract and the pancreas and lower than in tissue, leaving a poor sensitivity and specificity. Nevertheless, the presence of a p53 and/or ras mutation per se supports a clinical suspicion of malignancy, even when the conventional cytology is negative or inconclusive.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Low frequency of p53 and ras mutations in bile of patients with hepato‐biliary disease: a prospective study in more than 100 patients

Müller

Ostwald

Püschel

et al. 2001

Eur J Clin Investigation

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“…The incidence of Kras mutations in bile has been reported to range from 53% to 79%, 5,30,31 suggesting that K-ras mutation is a promising potential marker of BTCa. However, Ajiki et al 32 reported that K-ras codon 12 mutations were detected in 73% (8 of 11) of gallbladder dysplasias in patients with gallstone.…”

Section: Discussionmentioning

confidence: 99%

Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K- ras mutation

Wang

Yamaguchi

Watanabe

et al. 2002

Journal of Gastroenterology

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“…A wide range of figures have been reported with respect to activation by mutation of the K-ras gene in GBC. [80][81][82][83][84][85] There are authors who have not demonstrated any mutations in this gene; 36,86 others, however, have shown mutation in between 40 and 50% of GBCs. 83,86,87 Those patients with an anomalous arrangement of the pancreaticobiliary duct have a higher frequency of mutation of the K-ras gene than subjects without this condition.…”

Section: K-rasmentioning

confidence: 99%

“…A wide range of figures have been reported with respect to activation by mutation of the K‐ras gene in GBC 80–85 . There are authors who have not demonstrated any mutations in this gene; 36,86 others, however, have shown mutation in between 40 and 50% of GBCs 83,86,87 .…”

Section: K‐rasmentioning

confidence: 99%

Gallbladder cancer: a morphological and molecular update

2009

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Gallbladder cancer (GBC) shows a marked geographical variation in its incidence, with the highest figures being seen in India and Chile and relatively low levels in many Western countries. Risk factors for its development include the presence of gallstones, infection and the presence of an anomalous pancreatobiliary ductal junction. It can arise from either a pathway involving metaplasia or dysplasia or one in which there is a pre-existing adenoma. The former is the more common and, because it is often not associated with a macroscopically recognizable lesion, leads to the recommendation that all gallbladders need to be examined microscopically. Accurate staging of invasive cancers is essential to determine prognosis and treatment, and this requires extensive tumour sampling. A number of genetic alterations have been identified in the preinvasive and invasive stages of GBC and they support the morphological evidence of there being two pathways by which tumours develop. Some of these genetic changes are associated with particular risk factors. For example, cases with anomalous pancreatobiliary ductal junction show a higher frequency of K-ras mutations. Some changes are associated with differences in prognosis. For example, cancers without expression of p21 but with expression for p27 have a better prognosis, whereas those that express c-erb-B2 have a worse one. Work has also been done on identifying clinical, imaging and other factors that indicate that patients have a higher risk of having GBC. This is particularly important in high-incidence areas in which GBC is a significant public health problem.

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Usefulness of K-ras gene mutation at codon 12 in bile for diagnosing biliary strictures.

Cited by 9 publications

References 0 publications

Low frequency of p53 and ras mutations in bile of patients with hepato‐biliary disease: a prospective study in more than 100 patients

Low frequency of p53 and ras mutations in bile of patients with hepato‐biliary disease: a prospective study in more than 100 patients

Usefulness of p53 gene mutations in the supernatant of bile for diagnosis of biliary tract carcinoma: comparison with K- ras mutation

Gallbladder cancer: a morphological and molecular update

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