Differing rates of loss of Dpc4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts evidence for a biologic distinction

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

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Biliary tract carcinomas are clinically heterogeneous. It is not known if molecular heterogeneity underlies the clinical differences. METHODS. The authors evaluated 128 bile duct carcinomas, 88 of the distal common bile duct and 40 of more proximal origin (28 perihilar carcinomas, 12 intrahepatic carcinomas), immunohistochemically for abnormalities in the expression of the products of the DPC4 and p53 tumor-suppressor genes. Prognostic factors were evaluated in the series of distal bile duct carcinomas for which follow-up information was available. RESULTS. The authors found that a significantly higher percentage of distal bile duct carcinomas (55%) demonstrated loss of DPC4 expression than did the proximal bile duct carcinomas (15%; P < 0.001). They also found that a significantly higher percentage of the distal tumors abnormally expressed the p53 gene product (51% vs. 26%; P < 0.001). Among the distal common bile duct carcinomas, the presence of poorly differentiated histology correlated with decreased survival in multivariate analysis, while labeling for p53 or Dpc4, margin status, lymph node status, and tumor dimension did not correlate significantly with survival. CONCLUSIONS. These results demonstrate that abnormalities in DPC4 and p53 gene expression are frequent in distal common bile duct carcinomas, just as they are in pancreatic ductal adenocarcinoma, suggesting that these two tumor types might share a similar molecular pathogenesis. They also show that proximal and distal bile duct carcinomas have different patterns of inactivation of tumor-suppressor genes, indicating that they often arise through different molecular mechanisms likely reflecting their differing etiologies.

Original languageEnglish (US)
Pages (from-to)1332-1341
Number of pages10
JournalCancer
Volume91
Issue number7
DOIs
StatePublished - Apr 1 2001
Externally publishedYes

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Bile Ducts
Carcinoma
Common Bile Duct
p53 Genes
Tumor Suppressor Genes
Neoplasms
Biliary Tract
Histology
Adenocarcinoma
Multivariate Analysis
Lymph Nodes
Gene Expression

Keywords

  • Bile duct
  • Cholangiocarcinoma
  • DPC4
  • P53
  • Tumor-suppressor gene

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Differing rates of loss of Dpc4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts evidence for a biologic distinction. / 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.

In: Cancer, Vol. 91, No. 7, 01.04.2001, p. 1332-1341.

Research output: Contribution to journalArticle

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. / Differing rates of loss of Dpc4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts evidence for a biologic distinction. In: Cancer. 2001 ; Vol. 91, No. 7. pp. 1332-1341.
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title = "Differing rates of loss of Dpc4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts evidence for a biologic distinction",
abstract = "BACKGROUND. Biliary tract carcinomas are clinically heterogeneous. It is not known if molecular heterogeneity underlies the clinical differences. METHODS. The authors evaluated 128 bile duct carcinomas, 88 of the distal common bile duct and 40 of more proximal origin (28 perihilar carcinomas, 12 intrahepatic carcinomas), immunohistochemically for abnormalities in the expression of the products of the DPC4 and p53 tumor-suppressor genes. Prognostic factors were evaluated in the series of distal bile duct carcinomas for which follow-up information was available. RESULTS. The authors found that a significantly higher percentage of distal bile duct carcinomas (55{\%}) demonstrated loss of DPC4 expression than did the proximal bile duct carcinomas (15{\%}; P < 0.001). They also found that a significantly higher percentage of the distal tumors abnormally expressed the p53 gene product (51{\%} vs. 26{\%}; P < 0.001). Among the distal common bile duct carcinomas, the presence of poorly differentiated histology correlated with decreased survival in multivariate analysis, while labeling for p53 or Dpc4, margin status, lymph node status, and tumor dimension did not correlate significantly with survival. CONCLUSIONS. These results demonstrate that abnormalities in DPC4 and p53 gene expression are frequent in distal common bile duct carcinomas, just as they are in pancreatic ductal adenocarcinoma, suggesting that these two tumor types might share a similar molecular pathogenesis. They also show that proximal and distal bile duct carcinomas have different patterns of inactivation of tumor-suppressor genes, indicating that they often arise through different molecular mechanisms likely reflecting their differing etiologies.",
keywords = "Bile duct, Cholangiocarcinoma, DPC4, P53, Tumor-suppressor gene",
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TY - JOUR

T1 - Differing rates of loss of Dpc4 expression and of p53 overexpression among carcinomas of the proximal and distal bile ducts evidence for a biologic distinction

AU - Argani, Pedram

AU - Shaukat, Aasma

AU - Kaushal, Manju

AU - Wilentz, Robb E.

AU - Su, Gloria H.

AU - Sohn, Taylor A.

AU - Yeo, Charles J.

AU - Cameron, John L.

AU - Kern, Scott E.

AU - Hruban, Ralph H.

PY - 2001/4/1

Y1 - 2001/4/1

N2 - BACKGROUND. Biliary tract carcinomas are clinically heterogeneous. It is not known if molecular heterogeneity underlies the clinical differences. METHODS. The authors evaluated 128 bile duct carcinomas, 88 of the distal common bile duct and 40 of more proximal origin (28 perihilar carcinomas, 12 intrahepatic carcinomas), immunohistochemically for abnormalities in the expression of the products of the DPC4 and p53 tumor-suppressor genes. Prognostic factors were evaluated in the series of distal bile duct carcinomas for which follow-up information was available. RESULTS. The authors found that a significantly higher percentage of distal bile duct carcinomas (55%) demonstrated loss of DPC4 expression than did the proximal bile duct carcinomas (15%; P < 0.001). They also found that a significantly higher percentage of the distal tumors abnormally expressed the p53 gene product (51% vs. 26%; P < 0.001). Among the distal common bile duct carcinomas, the presence of poorly differentiated histology correlated with decreased survival in multivariate analysis, while labeling for p53 or Dpc4, margin status, lymph node status, and tumor dimension did not correlate significantly with survival. CONCLUSIONS. These results demonstrate that abnormalities in DPC4 and p53 gene expression are frequent in distal common bile duct carcinomas, just as they are in pancreatic ductal adenocarcinoma, suggesting that these two tumor types might share a similar molecular pathogenesis. They also show that proximal and distal bile duct carcinomas have different patterns of inactivation of tumor-suppressor genes, indicating that they often arise through different molecular mechanisms likely reflecting their differing etiologies.

AB - BACKGROUND. Biliary tract carcinomas are clinically heterogeneous. It is not known if molecular heterogeneity underlies the clinical differences. METHODS. The authors evaluated 128 bile duct carcinomas, 88 of the distal common bile duct and 40 of more proximal origin (28 perihilar carcinomas, 12 intrahepatic carcinomas), immunohistochemically for abnormalities in the expression of the products of the DPC4 and p53 tumor-suppressor genes. Prognostic factors were evaluated in the series of distal bile duct carcinomas for which follow-up information was available. RESULTS. The authors found that a significantly higher percentage of distal bile duct carcinomas (55%) demonstrated loss of DPC4 expression than did the proximal bile duct carcinomas (15%; P < 0.001). They also found that a significantly higher percentage of the distal tumors abnormally expressed the p53 gene product (51% vs. 26%; P < 0.001). Among the distal common bile duct carcinomas, the presence of poorly differentiated histology correlated with decreased survival in multivariate analysis, while labeling for p53 or Dpc4, margin status, lymph node status, and tumor dimension did not correlate significantly with survival. CONCLUSIONS. These results demonstrate that abnormalities in DPC4 and p53 gene expression are frequent in distal common bile duct carcinomas, just as they are in pancreatic ductal adenocarcinoma, suggesting that these two tumor types might share a similar molecular pathogenesis. They also show that proximal and distal bile duct carcinomas have different patterns of inactivation of tumor-suppressor genes, indicating that they often arise through different molecular mechanisms likely reflecting their differing etiologies.

KW - Bile duct

KW - Cholangiocarcinoma

KW - DPC4

KW - P53

KW - Tumor-suppressor gene

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DO - 10.1002/1097-0142(20010401)91:7<1332::AID-CNCR1136>3.0.CO;2-4

M3 - Article

VL - 91

SP - 1332

EP - 1341

JO - Cancer

JF - Cancer

SN - 0008-543X

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