Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas

Kondo, Hitoshi; Sugano, Kokichi; Fukayama, Noriko; Hosokawa, Koichi; Ohkura, H; Ohtsu, Atsushi; Mukai, Kiyoshi; Yoshida, Shigeaki

doi:10.1002/(sici)1097-0142(19970301)79:5<900::aid-cncr5>3.0.co;2-f

Cited by 80 publications

(34 citation statements)

References 19 publications

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“…17) K-ras point mutations in sediments of pancreatic juice have been detected in 6-31% of chronic pancreatitis and 25-89% of intraductal adenoma cases, according to previous reports. 2,13,28,34) Similarly, in the present study, 3/9 (33.3%) of chronic pancreatitis and 1/2 (50%) of intraductal adenoma cases were positive. Since mutations of K-ras oncogene occur not only in pancreatic adenocarcinoma, but also in other benign lesions, the possibility of false positives in chronic pancreatitis or ductal papillary hyperplasia or intraductal papillary adenoma 2,29,32,34,37) must be taken into account.…”

Section: Discussionsupporting

confidence: 77%

“…Further, all of the mutated ras genes found with PCR-SSCP were confirmed by direct sequencing. The present analysis using the supernatant with first or second PCR-SSCP showed almost equivalent or greater detection sensitivity as compared to previous studies 7,34) using the cell pellet or sediment with the enriched-PCR method. Since apoptosis of cancer cells is enhanced, together with cell proliferation, compared to that of normal cells, [34][35][36] nucleic acids originated from cancer cells shed from ducts may appear at relatively high concentration and be well preserved in the supernatant of pancreatic juice and bile.…”

Section: Discussionsupporting

confidence: 64%

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k‐ras Point Mutations in the Supernatants of Pancreatic Juice and Bile Are Reliable for Diagnosis of Pancreas and Biliary Tract Carcinomas Complementary to Cytologic Examination

Yamashita

Kida

Shinoda

et al. 1999

Japanese Journal of Cancer Research

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In order to clarify whether DNA analysis for K-ras mutation can be used to diagnose cancers in supernatants of pancreatic juice and bile, samples from 29 cases of pancreatic, biliary tract, gastric, and neuroendocrine carcinomas, 1 malignant lymphoma case, 2 cases of pancreatic adenoma, 9 cases of chronic pancreatitis and 21 other non-cancer cases were examined. Polymerase chain reaction (PCR) products for K-ras gene codons 2 to 97 of exons 1 and 2 were generated with 33/33 (100%) pancreatic juice and 41/41 (100%) bile samples. By the single strand conformation polymorphism (SSCP) method, point mutations were detected in the pancreatic juice or bile supernatants of 13/13 (100%) pancreas cancer cases, 5/14 (35.7%) biliary tract cancer cases, 1/2 (50.0%) pancreatic adenoma cases and 3/9 (33.3%) chronic pancreatitis cases. Direct sequencing confirmed identical point mutations in the supernatants, malignant cells of cytologic smears of pancreatic juice or bile and cancer tissues. The DNA analysis demonstrated the presence of K-ras point mutations in 3 cases of pancreatic carcinomas with false-negative cytologic diagnoses. This novel method allows simultaneous testing for genetic abnormalities in supernatants of pancreatic juice and bile, after removing cells for cytologic diagnosis and screening for pancreatic and biliary tract tumors.

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Section: Discussionsupporting

confidence: 77%

Section: Discussionsupporting

confidence: 64%

k‐ras Point Mutations in the Supernatants of Pancreatic Juice and Bile Are Reliable for Diagnosis of Pancreas and Biliary Tract Carcinomas Complementary to Cytologic Examination

Yamashita

Kida

Shinoda

et al. 1999

Japanese Journal of Cancer Research

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“…11,12 Recently some reports have encouraged the establishment of molecular diagnosis by using K-ras, p53, p16(INK4A), Smad4, telomerase activity, and the expression of MUC1. [13][14][15][16][17][18] However, these techniques are not yet practically useful.…”

Section: Discussionmentioning

confidence: 99%

Multicenter Analysis of Clinicopathologic Features of Intraductal Papillary Mucinous Tumor of the Pancreas: Is It Possible to Predict the Malignancy Before Surgery?

et al. 2005

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Background: Despite recently increasing numbers of reports on intraductal papillary mucinous tumors (IPMTs), difficulties still remain in terms of diagnosis, treatment, and prognosis. The purpose of this multicenter study was to evaluate the clinicopathologic features of IPMT in Korea and to suggest predictive criteria for malignancy in IPMT.Methods: We retrospectively reviewed the clinicopathologic data of 208 patients who underwent operations for IPMT between 1993 and 2002 at 28 institutes in Korea.Results: Of the 208 patients (mean age, 61 years), 147 were men and 61 were women. A total of 124 patients underwent pancreatoduodenectomy, 42 underwent distal pancreatectomy, 17 underwent total pancreatectomy, and 25 underwent limited pancreatic resection. There were 128 benign cases (adenoma, n = 62; borderline, n = 66) and 80 malignant cases (noninvasive, n = 29; invasive, n = 51). A significant difference in 5-year survival was observed between the benign and malignant groups (92.6% vs. 65.3%; P = .006). Of the six factors (age, location, duct dilatation, mural nodule, main duct type, and tumor size) that showed statistical dif-

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“…Detection of KRAS2 mutations were first reported in surgically removed pancreatic tumoural tissue or at autopsy (Almoguera et al, 1988;Tada et al, 1991). Thereafter mutations were discovered in 63 to 83% of samples of pure pancreatic juice or main pancreatic duct brushing obtained during endoscopic retrograde pancreatography (Iguchi et al, 1996;Kondo et al, 1997;Tada et al, 1998;Van Laethem et al, 1998;Okai et al, 1999;Watanabe et al, 1999;Ha et al, 2001;Pugliese et al, 2001;Seki et al, 2001) or at fine-needle tumour aspiration (Pabst et al, 1999;Puig et al, 2000), and in 20 to 54% of stools (Caldas et al, 1994;Wenger et al, 1999) from patients with pancreatic cancer. Circulating deoxyribo nucleic acid (DNA) was first detected in serum or plasma of normal subjects in 1975 (Steinman, 1975).…”

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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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Detection of K-ras gene mutations at codon 12 in the pancreatic juice of patients with intraductal papillary mucinous tumors of the pancreas

Cited by 80 publications

References 19 publications

k‐ras Point Mutations in the Supernatants of Pancreatic Juice and Bile Are Reliable for Diagnosis of Pancreas and Biliary Tract Carcinomas Complementary to Cytologic Examination

k‐ras Point Mutations in the Supernatants of Pancreatic Juice and Bile Are Reliable for Diagnosis of Pancreas and Biliary Tract Carcinomas Complementary to Cytologic Examination

Multicenter Analysis of Clinicopathologic Features of Intraductal Papillary Mucinous Tumor of the Pancreas: Is It Possible to Predict the Malignancy Before Surgery?

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

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