Ductal lesions in patients with chronic pancreatitis show K-ras mutations in a frequency similar to that in the normal pancreas and lack nuclear immunoreactivity for p53

Lüttges, Jutta; Diederichs, Anke; Menke, Martin A. O. H.; Vogel, Ilka; Kremer, Bernd; Klöppel, Günter

doi:10.1002/1097-0142(20000601)88:11<2495::aid-cncr10>3.0.co;2-b

Cited by 81 publications

(48 citation statements)

References 37 publications

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“…Three studies have reported a higher specificity of serum KRAS2 mutations compared to the current study (100 vs 87%), but their control groups included few patients and essentially healthy subjects (Mulcahy et al, 1998;Porta et al, 1999;Theodor et al, 2000). Since KRAS2 mutations have been reported in pancreatic tissue or juice from 6 -42% of patients with chronic pancreatitis (Furuya et al, 1997;Mulligan et al, 1999;Lüttges et al, 2000;Ha et al, 2001), and knowing that a part of this mutated DNA can be released into circulation (Yamada et al, 1998), the control group should include patients with chronic pancreatitis. In the series published by Castells et al (1999) with the largest control group (including patients with chronic pancreatitis), specificity was comparable (94%) to the present study, and increased in the presence of a pancreatic mass.…”

Section: Molecular and Cellular Pathologymentioning

confidence: 63%

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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Section: Molecular and Cellular Pathologymentioning

confidence: 63%

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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“…Non-specific cytoplasmic staining with either CEA or CA19-9 has previously been demonstrated in both the normal and inflamed pancreatic ductal epithelium [35][36][37] . Performance was poor for all the markers when used as indicators for the absence of malignancy (alone or in various parallel combinations of up to four markers) as demonstrated by low NPVs and non-significant NLRs.…”

Section: Discussionmentioning

confidence: 99%

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

Jahng

Reicher²,

Chung³

et al. 2010

WJGE

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AIM:To investigate whether tumor marker staining can improve the sensitivity of endoscopic ultrasound-guided fine needle aspiration (EUS-FNA) to diagnose pancreatic malignancy. METHODS:Patients who underwent EUS-FNA were retrospectively identified. Each EUS-FNA specimen was evaluated by routine cytology and stained for tumor markers p53, Ki-67, carcinoembryonic antigen (CEA) and CA19-9. Sensitivity, specificity, positive and negative predictive values (PPV and NPV), and positive and negative likelihood ratios (PLR and NLR) were calculated in order to evaluate the performance of each test to detect malignancy. RESULTS:Sixty-one specimens had complete sets of stains, yielding 49 and 12 specimens from pancreatic adenocarcinomas and benign pancreatic lesions due to pancreatitis, respectively. Cytology alone had sensitivity and specificity of 41% and 100% to detect malignancy, respectively. In 46% of the specimens, routine cytology alone was deemed indeterminate. The addition of either p53 or Ki-67 increased the sensitivity to 51% and 53%, respectively, with perfect specificity, PPV and PLR (100%, 100% and infinite). Both stains in combination increased the sensitivity to 57%. While additional staining with CEA and CA19-9 further increased the sensitivity to 86%, the specificity, PPV and PLR were significantly reduced (at minimum 42%, 84% and 1, respectively). Markers in all combinations performed poorly as a negative test (NPV 26% to 47%, and NLR 0.27 and 0.70). CONCLUSION: Immunohistochemical staining for p53and Ki-67 can improve the sensitivity of EUS-FNA to diagnose pancreatic adenocarcinoma.

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“…The median percentage of total, visceral, and SFA (regarding the total surface of the slide) represented: 21% (2-47), 7.3% (0. [8][9][10][11][12][13][14][15][16][17][18][19][20], and 13% (1.2-31.7), respectively. Liver steatosis was observed in 27%.…”

Section: Radiologic Characteristicsmentioning

confidence: 99%

Obesity and Fatty Pancreatic Infiltration Are Risk Factors for Pancreatic Precancerous Lesions (PanIN)

Rebours

Gaujoux

d’Assignies

et al. 2015

Clinical Cancer Research

177

107

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Purpose: The roles of intravisceral and subcutaneous fat are unknown, and the prevalence of precancerous lesions in obese patients was never evaluated. This study aims to assess the frequency and severity of pancreatic intraepithelial neoplasia (PanIN) and to correlate pathologic findings with metabolic abnormalities, type of fat, and fatty pancreatic infiltration.Experimental Design: Normal pancreatic tissue from surgical specimens was analyzed. Fatty infiltration and fibrosis in intraand extralobular locations and PanIN lesions were assessed. General characteristics were collected: body mass index (BMI), diabetes, and tobacco intake. Liver steatosis and subcutaneous and intravisceral fat were assessed by CT scan (ImageJ software).Results: Of note, 110 patients were included [median age, 53.8 (17-85) years]. Arterial hypertension, diabetes, and tobacco intake were found in 19%, 9%, and 23%, respectively. Median BMI was 24 (16-37; BMI < 25: 45%, 25 30: 24%, !30: 11%). Overall, PanIN lesions were found in 65% (type I, II, and III PanIN in 62%, 38%, and 1%, respectively). Fibrosis and fatty pancreas (intra-and extralobular locations) were found in 1% and 24% and in 30% and 51%, respectively. A correlation was observed between PanIN lesions and fatty pancreas [extralobular (0.01) and intralobular (<0.0001)], intralobular fibrosis (0.003), high BMI (P ¼ 0.02), and subcutaneous (P ¼ 0.02) and intravisceral fat (P ¼ 0.02). The number of PanIN lesions was correlated with intravisceral fat (r ¼ 0.22, P ¼ 0.04), but not with subcutaneous fat (r ¼ 0.14, P ¼ 0.22). In multivariate analysis, PanIN lesions were associated with intralobular fibrosis [OR, 5.61; 95% confidence interval (CI), 1.18-42.99] and intralobular fat (OR, 17.86; 95% CI,.Conclusions: Obesity (especially android obesity) and pancreatic fatty infiltration are risk factors for pancreatic precancerous lesions.

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Ductal lesions in patients with chronic pancreatitis show K-ras mutations in a frequency similar to that in the normal pancreas and lack nuclear immunoreactivity for p53

Cited by 81 publications

References 37 publications

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

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

Staining for p53 and Ki-67 increases the sensitivity of EUS-FNA to detect pancreatic malignancy

Obesity and Fatty Pancreatic Infiltration Are Risk Factors for Pancreatic Precancerous Lesions (PanIN)

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