Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas

Comparison with conventional ductal adenocarcinomas

C. A. Iacobuzio-Donahue, D. S. Klimstra, N. V. Adsay, R. E. Wilentz, P. Argani, T. A. Sohn, C. J. Yeo, J. L. Cameron, S. E. Kern, R. H. Hruban

Research output: Contribution to journalArticle

209 Citations (Scopus)

Abstract

DPC4 (MADH4, SMAD4) encodes a nuclear transcription factor shown to be genetically inactivated in over one-half of conventional infiltrating ductal adenocarcinomas of the pancreas. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been suggested to be distinct neoplasms with a significantly less aggressive course than conventional ductal adenocarcinomas of the pancreas, but molecular comparisons of these tumor types have previously been impaired by technical difficulties. Recently, immunohistochemical labeling for the DPC4 gene product has been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Therefore, we analyzed the immunohistochemical expression of Dpc4 protein in 79 IPMNs using a previously characterized monoclonal antibody. Twenty-nine of the IPMNs also had an associated infiltrating adenocarcinoma available for analysis. The labeling patterns observed were compared to those we have previously reported for conventional ductal carcinomas. All 79 of the intraductal components of the IPMNs strongly expressed Dpc4 protein. In 77 of the 79 cases (97%), the labeling was diffusely positive, and in 2 of the 79 (3%) the labeling was focally positive. Dpc4 expression was seen in 28 (97%) of the associated 29 invasive cancers. The one infiltrating carcinoma that showed loss of Dpc4 expression was associated with an intraductal component which showed focal loss of Dpc4 expression. The strong and almost universal expression of Dpc4 in IPMNs contrasts sharply with the loss of Dpc4 expression seen in approximately 30% of in situ adenocarcinomas of the pancreas (so-called pancreatic intraepithelial neoplasms, grade 3; P < 0.001) and in 55% of pancreatic duct carcinomas (P < 0.0001). Differences in Dpc4 expression between IPMNs and ductal carcinomas suggest a fundamental genetic difference in tumorigenesis, which may relate to the significantly better clinical outcomes observed for IPMNs.

Original languageEnglish (US)
Pages (from-to)755-761
Number of pages7
JournalAmerican Journal of Pathology
Volume157
Issue number3
StatePublished - 2000
Externally publishedYes

Fingerprint

Pancreatic Neoplasms
Adenocarcinoma
Neoplasms
Proteins
Pancreas
Ductal Carcinoma
Mucinous Adenocarcinoma
Pancreatic Ducts
Papillary Carcinoma
Carcinoma in Situ
Genes
Carcinogenesis
Transcription Factors
Monoclonal Antibodies
Carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Iacobuzio-Donahue, C. A., Klimstra, D. S., Adsay, N. V., Wilentz, R. E., Argani, P., Sohn, T. A., ... Hruban, R. H. (2000). Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: Comparison with conventional ductal adenocarcinomas. American Journal of Pathology, 157(3), 755-761.

Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas : Comparison with conventional ductal adenocarcinomas. / Iacobuzio-Donahue, C. A.; Klimstra, D. S.; Adsay, N. V.; Wilentz, R. E.; Argani, P.; Sohn, T. A.; Yeo, C. J.; Cameron, J. L.; Kern, S. E.; Hruban, R. H.

In: American Journal of Pathology, Vol. 157, No. 3, 2000, p. 755-761.

Research output: Contribution to journalArticle

Iacobuzio-Donahue, CA, Klimstra, DS, Adsay, NV, Wilentz, RE, Argani, P, Sohn, TA, Yeo, CJ, Cameron, JL, Kern, SE & Hruban, RH 2000, 'Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: Comparison with conventional ductal adenocarcinomas', American Journal of Pathology, vol. 157, no. 3, pp. 755-761.
Iacobuzio-Donahue, C. A. ; Klimstra, D. S. ; Adsay, N. V. ; Wilentz, R. E. ; Argani, P. ; Sohn, T. A. ; Yeo, C. J. ; Cameron, J. L. ; Kern, S. E. ; Hruban, R. H. / Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas : Comparison with conventional ductal adenocarcinomas. In: American Journal of Pathology. 2000 ; Vol. 157, No. 3. pp. 755-761.
@article{e306f32ad5a742ce9574433729867be6,
title = "Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas: Comparison with conventional ductal adenocarcinomas",
abstract = "DPC4 (MADH4, SMAD4) encodes a nuclear transcription factor shown to be genetically inactivated in over one-half of conventional infiltrating ductal adenocarcinomas of the pancreas. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been suggested to be distinct neoplasms with a significantly less aggressive course than conventional ductal adenocarcinomas of the pancreas, but molecular comparisons of these tumor types have previously been impaired by technical difficulties. Recently, immunohistochemical labeling for the DPC4 gene product has been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Therefore, we analyzed the immunohistochemical expression of Dpc4 protein in 79 IPMNs using a previously characterized monoclonal antibody. Twenty-nine of the IPMNs also had an associated infiltrating adenocarcinoma available for analysis. The labeling patterns observed were compared to those we have previously reported for conventional ductal carcinomas. All 79 of the intraductal components of the IPMNs strongly expressed Dpc4 protein. In 77 of the 79 cases (97{\%}), the labeling was diffusely positive, and in 2 of the 79 (3{\%}) the labeling was focally positive. Dpc4 expression was seen in 28 (97{\%}) of the associated 29 invasive cancers. The one infiltrating carcinoma that showed loss of Dpc4 expression was associated with an intraductal component which showed focal loss of Dpc4 expression. The strong and almost universal expression of Dpc4 in IPMNs contrasts sharply with the loss of Dpc4 expression seen in approximately 30{\%} of in situ adenocarcinomas of the pancreas (so-called pancreatic intraepithelial neoplasms, grade 3; P < 0.001) and in 55{\%} of pancreatic duct carcinomas (P < 0.0001). Differences in Dpc4 expression between IPMNs and ductal carcinomas suggest a fundamental genetic difference in tumorigenesis, which may relate to the significantly better clinical outcomes observed for IPMNs.",
author = "Iacobuzio-Donahue, {C. A.} and Klimstra, {D. S.} and Adsay, {N. V.} and Wilentz, {R. E.} and P. Argani and Sohn, {T. A.} and Yeo, {C. J.} and Cameron, {J. L.} and Kern, {S. E.} and Hruban, {R. H.}",
year = "2000",
language = "English (US)",
volume = "157",
pages = "755--761",
journal = "American Journal of Pathology",
issn = "0002-9440",
publisher = "Elsevier Inc.",
number = "3",

}

TY - JOUR

T1 - Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas

T2 - Comparison with conventional ductal adenocarcinomas

AU - Iacobuzio-Donahue, C. A.

AU - Klimstra, D. S.

AU - Adsay, N. V.

AU - Wilentz, R. E.

AU - Argani, P.

AU - Sohn, T. A.

AU - Yeo, C. J.

AU - Cameron, J. L.

AU - Kern, S. E.

AU - Hruban, R. H.

PY - 2000

Y1 - 2000

N2 - DPC4 (MADH4, SMAD4) encodes a nuclear transcription factor shown to be genetically inactivated in over one-half of conventional infiltrating ductal adenocarcinomas of the pancreas. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been suggested to be distinct neoplasms with a significantly less aggressive course than conventional ductal adenocarcinomas of the pancreas, but molecular comparisons of these tumor types have previously been impaired by technical difficulties. Recently, immunohistochemical labeling for the DPC4 gene product has been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Therefore, we analyzed the immunohistochemical expression of Dpc4 protein in 79 IPMNs using a previously characterized monoclonal antibody. Twenty-nine of the IPMNs also had an associated infiltrating adenocarcinoma available for analysis. The labeling patterns observed were compared to those we have previously reported for conventional ductal carcinomas. All 79 of the intraductal components of the IPMNs strongly expressed Dpc4 protein. In 77 of the 79 cases (97%), the labeling was diffusely positive, and in 2 of the 79 (3%) the labeling was focally positive. Dpc4 expression was seen in 28 (97%) of the associated 29 invasive cancers. The one infiltrating carcinoma that showed loss of Dpc4 expression was associated with an intraductal component which showed focal loss of Dpc4 expression. The strong and almost universal expression of Dpc4 in IPMNs contrasts sharply with the loss of Dpc4 expression seen in approximately 30% of in situ adenocarcinomas of the pancreas (so-called pancreatic intraepithelial neoplasms, grade 3; P < 0.001) and in 55% of pancreatic duct carcinomas (P < 0.0001). Differences in Dpc4 expression between IPMNs and ductal carcinomas suggest a fundamental genetic difference in tumorigenesis, which may relate to the significantly better clinical outcomes observed for IPMNs.

AB - DPC4 (MADH4, SMAD4) encodes a nuclear transcription factor shown to be genetically inactivated in over one-half of conventional infiltrating ductal adenocarcinomas of the pancreas. Intraductal papillary mucinous neoplasms (IPMNs) of the pancreas have been suggested to be distinct neoplasms with a significantly less aggressive course than conventional ductal adenocarcinomas of the pancreas, but molecular comparisons of these tumor types have previously been impaired by technical difficulties. Recently, immunohistochemical labeling for the DPC4 gene product has been shown to be an extremely sensitive and specific marker for DPC4 gene alterations in pancreatic adenocarcinomas. Therefore, we analyzed the immunohistochemical expression of Dpc4 protein in 79 IPMNs using a previously characterized monoclonal antibody. Twenty-nine of the IPMNs also had an associated infiltrating adenocarcinoma available for analysis. The labeling patterns observed were compared to those we have previously reported for conventional ductal carcinomas. All 79 of the intraductal components of the IPMNs strongly expressed Dpc4 protein. In 77 of the 79 cases (97%), the labeling was diffusely positive, and in 2 of the 79 (3%) the labeling was focally positive. Dpc4 expression was seen in 28 (97%) of the associated 29 invasive cancers. The one infiltrating carcinoma that showed loss of Dpc4 expression was associated with an intraductal component which showed focal loss of Dpc4 expression. The strong and almost universal expression of Dpc4 in IPMNs contrasts sharply with the loss of Dpc4 expression seen in approximately 30% of in situ adenocarcinomas of the pancreas (so-called pancreatic intraepithelial neoplasms, grade 3; P < 0.001) and in 55% of pancreatic duct carcinomas (P < 0.0001). Differences in Dpc4 expression between IPMNs and ductal carcinomas suggest a fundamental genetic difference in tumorigenesis, which may relate to the significantly better clinical outcomes observed for IPMNs.

UR - http://www.scopus.com/inward/record.url?scp=0034495006&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034495006&partnerID=8YFLogxK

M3 - Article

VL - 157

SP - 755

EP - 761

JO - American Journal of Pathology

JF - American Journal of Pathology

SN - 0002-9440

IS - 3

ER -