Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia

Evidence that DPC4 inactivation occurs late in neoplastic progression

Robb E. Wilentz, Christine A. Iacobuzio-Donahue, Pedram Argani, Denis M. McCarthy, Jennifer L. Parsons, Charles J. Yeo, Scott E Kern, Ralph H Hruban

Research output: Contribution to journalArticle

Abstract

Infiltrating adenocarcinomas of the pancreas are believed to arise from histologically identifiable intraductal precursors [pancreatic intraepithelial neoplasias (PanINs)] that undergo a series of architectural, cytological, and genetic changes. The role of DPC4 tumor suppressor gene inactivation in this progression has not been defined. Immunohistochemistry for the Dpc4 protein in formalin-fixed, paraffin-embedded tissue is a sensitive and specific marker for DPC4 gene status, providing a tool to examine DPC4 status in these putative precursor lesions. A total of 188 PanINs were identified in 40 pancreata, 38 (95%) of which also contained an infiltrating adenocarcinoma. Sections containing these 188 duct lesions were labeled with a monoclonal antibody to Dpc4. All 82 flat (PanIN-1A), all 54 papillary (PaniN-1B), and all 23 atypical papillary (PanIN-2) intraductal lesions expressed Dpc4. In contrast, 9 of 29 (31%) severely atypical lesions (PanIN-3 lesions, carcinomas in situ) did not. The difference in Dpc4 expression between histologically low-grade (PanIN-1 and -2) and histologically high-grade (PanIN-3) duct lesions was statistically significant (P <0.0001). In three cases, the pattern of Dpc4 expression in the PanIN-3 lesions did not match the pattern of expression in the associated infiltrating carcinomas, indicating that these high-grade lesions did not simply represent infiltrating carcinoma growing along benign ducts. Loss of Dpc4 expression occurs biologically late in the neoplastic progression that leads to the development of infiltrating pancreatic cancer, at the stage of histologically recognizable carcinoma.

Original languageEnglish (US)
Pages (from-to)2002-2006
Number of pages5
JournalCancer Research
Volume60
Issue number7
StatePublished - Apr 1 2000

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Carcinoma
Pancreas
Adenocarcinoma
Neoplasms
Carcinoma in Situ
Gene Silencing
Tumor Suppressor Genes
Pancreatic Neoplasms
Paraffin
Formaldehyde
Immunohistochemistry
Monoclonal Antibodies
Genes
Proteins

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia : Evidence that DPC4 inactivation occurs late in neoplastic progression. / Wilentz, Robb E.; Iacobuzio-Donahue, Christine A.; Argani, Pedram; McCarthy, Denis M.; Parsons, Jennifer L.; Yeo, Charles J.; Kern, Scott E; Hruban, Ralph H.

In: Cancer Research, Vol. 60, No. 7, 01.04.2000, p. 2002-2006.

Research output: Contribution to journalArticle

Wilentz, Robb E. ; Iacobuzio-Donahue, Christine A. ; Argani, Pedram ; McCarthy, Denis M. ; Parsons, Jennifer L. ; Yeo, Charles J. ; Kern, Scott E ; Hruban, Ralph H. / Loss of expression of Dpc4 in pancreatic intraepithelial neoplasia : Evidence that DPC4 inactivation occurs late in neoplastic progression. In: Cancer Research. 2000 ; Vol. 60, No. 7. pp. 2002-2006.
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abstract = "Infiltrating adenocarcinomas of the pancreas are believed to arise from histologically identifiable intraductal precursors [pancreatic intraepithelial neoplasias (PanINs)] that undergo a series of architectural, cytological, and genetic changes. The role of DPC4 tumor suppressor gene inactivation in this progression has not been defined. Immunohistochemistry for the Dpc4 protein in formalin-fixed, paraffin-embedded tissue is a sensitive and specific marker for DPC4 gene status, providing a tool to examine DPC4 status in these putative precursor lesions. A total of 188 PanINs were identified in 40 pancreata, 38 (95{\%}) of which also contained an infiltrating adenocarcinoma. Sections containing these 188 duct lesions were labeled with a monoclonal antibody to Dpc4. All 82 flat (PanIN-1A), all 54 papillary (PaniN-1B), and all 23 atypical papillary (PanIN-2) intraductal lesions expressed Dpc4. In contrast, 9 of 29 (31{\%}) severely atypical lesions (PanIN-3 lesions, carcinomas in situ) did not. The difference in Dpc4 expression between histologically low-grade (PanIN-1 and -2) and histologically high-grade (PanIN-3) duct lesions was statistically significant (P <0.0001). In three cases, the pattern of Dpc4 expression in the PanIN-3 lesions did not match the pattern of expression in the associated infiltrating carcinomas, indicating that these high-grade lesions did not simply represent infiltrating carcinoma growing along benign ducts. Loss of Dpc4 expression occurs biologically late in the neoplastic progression that leads to the development of infiltrating pancreatic cancer, at the stage of histologically recognizable carcinoma.",
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T2 - Evidence that DPC4 inactivation occurs late in neoplastic progression

AU - Wilentz, Robb E.

AU - Iacobuzio-Donahue, Christine A.

AU - Argani, Pedram

AU - McCarthy, Denis M.

AU - Parsons, Jennifer L.

AU - Yeo, Charles J.

AU - Kern, Scott E

AU - Hruban, Ralph H

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