Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts

Argani, Pedram; Shaukat, Aasma; Kaushal, Manju; Wilentz, Robb E.; Su, Gloria H.; Sohn, Taylor A.; Yeo, Charles J.; Cameron, John L.; Kern, Scott E.; Hruban, Ralph H.

doi:10.1002/1097-0142(20010401)91:7<1332::aid-cncr1136>3.3.co;2-w

Cited by 31 publications

(45 citation statements)

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“…In two studies of DPC4 protein expression, loss was noted in 55% and 60% of extra-hepatic bile duct carcinomas. However, there was no correlation with survival (17,30).…”

Section: P53 [Table 1]supporting

confidence: 90%

“…A number of factors may account for these disparities including use of different cut-off values for positivity, antibodies and inclusion of varying anatomical and histological subtypes of CC. Indeed, two studies have noted increasing p53 expression in more distal tumours in comparison to proximal ones when a subanalysis is undertaken (28,30). This may indicate a more important role for p53 overexpression in extra-hepatic, distal bile duct carcinomas.…”

Section: P53 [Table 1]mentioning

confidence: 87%

“…A number of groups found an association with decreased overall survival (11,12,(25)(26)(27)(28), but only one of these has demonstrated independent prognostic significance (29). However, in a large series Argani et al showed increased overall survival in their p53 positive group (30). A number of factors may account for these disparities including use of different cut-off values for positivity, antibodies and inclusion of varying anatomical and histological subtypes of CC.…”

Section: P53 [Table 1]mentioning

confidence: 99%

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Prognostic molecular markers in cholangiocarcinoma: A systematic review

Briggs

Neal

Mann

et al. 2009

European Journal of Cancer

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The worldwide incidence of cholangiocarcinoma (CC) is steadily rising, the United Kingdom incidence now exceeding 1000 cases per year. It is an aggresive malignancy typified by unresponsiveness to existing chemotherapy and radiotherapy regimes in the vast majority of cases. Surgery offers the only hope of a cure, though postoperative disease recurrence is common, with 5-year survival rates following resection of less then 25%. Developments in molecular techniques and improved understanding of the basis of carcinogenesis in CC has led to examination of the role of biomarkers in predicting poor outcome. This systematic review examines published evidence relating to the prognostic significance of these molecular markers in CC. Of the molecular markers which have been investigated to date p53 mutation, cyclins, proliferation indices, mucins, CA19-9, CRP, and aneuploidy appear to hold significant potential as predictors of outcome in CC. These and other biomarkers may themselves represent novel therapeutic targets for CC.

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“…In two studies of DPC4 protein expression, loss was noted in 55% and 60% of extra-hepatic bile duct carcinomas. However, there was no correlation with survival (17,30).…”

Section: P53 [Table 1]supporting

confidence: 90%

Section: P53 [Table 1]mentioning

confidence: 87%

Section: P53 [Table 1]mentioning

confidence: 99%

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Prognostic molecular markers in cholangiocarcinoma: A systematic review

Briggs

Neal

Mann

et al. 2009

European Journal of Cancer

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“…Previously, we showed that loss of Dpc4 expression is as frequent in distal (intrapancreatic) bile duct carcinomas (55%) as it is in pancreatic adenocarcinoma. In contrast, the frequency of Dpc4 loss was lower (overall, 15%) in more proximal (perihilar and intrahepatic) bile duct carcinomas (28). Interestingly, we observed loss of Dpc4 protein in a similar percentage of in situ gallbladder carcinomas associated with invasive carcinomas (2 of 13, or 15%), suggesting that DPC4 inactivation occurs early in these lesions.…”

Section: Discussionmentioning

confidence: 99%

Immunohistochemical and Genetic Analysis of Non–Small Cell and Small Cell Gallbladder Carcinoma and Their Precursor Lesions

et al. 2003

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Gallbladder carcinomas can be highly lethal neoplasms. Relatively little is known about the genetic abnormalities that underlie these tumors, particularly with respect to their timing in neoplastic progression. The authors evaluated 5 noninvasive dysplasias and 33 invasive gallbladder carcinomas (6 small cell carcinomas, 27 non-small cell carcinomas, of which 16 were accompanied by an in situ carcinoma component) for expression of the protein products of the p16, p53, Dpc4, and pRB tumor suppressor genes by immunohistochemistry. Neoplasms were also evaluated for the presence of activating K-ras oncogene mutations. Seventy-five percent of non-small cell gallbladder carcinomas demonstrated loss of p16 expression, whereas 63% accumulated high levels of p53. Loss of Dpc4 and pRB expression was less frequent, seen in 19% and 4% of the neoplasms, respectively. Thirty percent of neoplasms harbored activating K-ras mutations. In contrast, 100% of the small cell carcinomas of the gallbladder demonstrated inactivation of the pRB/ p16 pathway; 67% showed loss of pRB expression, and the other 33% lost p16 expression. Eighty-three percent of small cell carcinomas accumulated high levels of p53, whereas loss of Dpc4 expression and activating K-ras mutations were not found. Among 15 evaluable in situ components, 13 harbored the same alterations found in the invasive component.Inactivation of p16 and p53 occur in the majority of non-small cell gallbladder carcinomas. Dpc4 inactivation and K-ras mutations occur in a significant minority of cases. pRB loss is uncommon in nonsmall cell gallbladder carcinoma, but virtually all small cell carcinomas inactivate the p16/pRB pathway, usually by retinoblastoma protein loss. It is noteworthy that all of these alterations occur at the level of carcinoma in situ.

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“…Loss of expression is seen in approximately 60% of pancreatic ductal adenocarcinomas, which is associated with poor prognosis. 162,192 SMAD4 loss is also reported in 9.5% of gallbladder adenocarcinomas, 193 50% to 55% adenocarcinomas of extrahepatic bile ducts, 193,194 and 12.5% to 45% intrahepatic cholangiocarcinomas. [193][194][195] CK17.-Cytoplasmic CK17 positivity has been reported in 60% to 88% of pancreatic ductal adenocarcinomas, 162,167,196,197 53% of gallbladder adenocarcinomas, 198 and 59% of adenocarcinomas of extrahepatic bile ducts.…”

mentioning

confidence: 99%

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

Wang¹,

Kim²,

Koo³

et al. 2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Immunomarkers with diagnostic, therapeutic, or prognostic values have been increasingly used to maximize the benefits of clinical management of patients with neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Objectives.— To review the characteristics of immunomarkers that are commonly used in surgical pathology practice for neoplasms of the gastrointestinal tract, liver, biliary tract, and pancreas, and to summarize the clinical usefulness of immunomarkers that have been discovered in recent years in these fields. Data Sources.— Data sources include literature review, authors' research data, and personal practice experience. Conclusions.— Immunohistochemistry is an indispensable tool for the accurate diagnosis of neoplastic diseases of the gastrointestinal tract, liver, biliary tract, and pancreas. Useful immunomarkers are available to help distinguish malignant neoplasms from benign conditions, determine organ origins, and subclassify neoplasms that are morphologically and biologically heterogeneous. Specific immunomarkers are also available to help guide patient treatment and assess disease aggressiveness, which are keys to the success of personalized medicine. Pathologists will continue to play a critical role in the discovery, validation, and application of new biomarkers, which will ultimately improve patient care.

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Differing rates of loss of DPC4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts

Cited by 31 publications

References 0 publications

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Prognostic molecular markers in cholangiocarcinoma: A systematic review

Immunohistochemical and Genetic Analysis of Non–Small Cell and Small Cell Gallbladder Carcinoma and Their Precursor Lesions

Practical Immunohistochemistry in Neoplastic Pathology of the Gastrointestinal Tract, Liver, Biliary Tract, and Pancreas

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