Dpc-4 protein is expressed in virtually all human intraductal papillary mucinous neoplasms of the pancreas - Comparison with conventional ductal adenocarcinomas

被引:156
作者
Iacobuzio-Donahue, CA
Klimstra, DS
Adsay, NV
Wilentz, RE
Argani, P
Sohn, TA
Yeo, CJ
Cameron, JL
Kern, SE
Hruban, RH
机构
[1] Johns Hopkins Med Inst, Dept Pathol, Baltimore, MD 21205 USA
[2] Johns Hopkins Med Inst, Dept Surg, Baltimore, MD 21205 USA
[3] Johns Hopkins Med Inst, Dept Oncol, Baltimore, MD 21205 USA
[4] Mem Sloan Kettering Canc Ctr, Dept Pathol, New York, NY 10021 USA
[5] Wayne State Univ, Dept Pathol, Detroit, MI 48202 USA
关键词
D O I
10.1016/S0002-9440(10)64589-0
中图分类号
R36 [病理学];
学科分类号
100104 ;
摘要
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.
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页码:755 / 761
页数:7
相关论文
共 42 条
[1]   Intraductal oncocytic papillary neoplasms of the pancreas [J].
Adsay, NV ;
Adair, CF ;
Heffess, CS ;
Klimstra, DS .
AMERICAN JOURNAL OF SURGICAL PATHOLOGY, 1996, 20 (08) :980-994
[2]   Intraductal papillary mucinous tumours of the pancreas. Clinical and therapeutic issues in 32 patients [J].
Azar, C ;
VandeStadt, J ;
Rickaert, F ;
Deviere, J ;
Delhaye, M ;
Baize, M ;
Kloppel, G ;
Gelin, M ;
Cremer, M .
GUT, 1996, 39 (03) :457-464
[3]   DIFFUSE INTRADUCTAL PAPILLARY ADENOCARCINOMA OF THE PANCREAS [J].
CONLEY, CR ;
SCHEITHAUER, BW ;
VANHEERDEN, JA ;
WEILAND, LH .
ANNALS OF SURGERY, 1987, 205 (03) :246-249
[4]  
Dai JL, 1999, MOL CARCINOGEN, V26, P37, DOI 10.1002/(SICI)1098-2744(199909)26:1<37::AID-MC5>3.0.CO
[5]  
2-6
[6]  
Dai JL, 1998, CANCER RES, V58, P4592
[7]   DPC4 (SMAD4) mediates transforming growth factor-beta 1 (TGF-beta 1) induced growth inhibition and transcriptional response in breast tumour cells [J].
deWinter, JP ;
Roelen, BAJ ;
tenDijke, P ;
vanderBurg, B ;
vandenEijndenvanRaaij, A .
ONCOGENE, 1997, 14 (16) :1891-1899
[8]  
Fujii H, 1997, AM J PATHOL, V151, P1447
[9]   Intraductal papillary tumors and mucinous cystic tumors of the pancreas: Clinicopathologic study of 38 cases [J].
Fukushima, N ;
Mukai, K ;
Kanai, Y ;
Hasebe, T ;
Shimada, K ;
Ozaki, H ;
Kinoshita, T ;
Kosuge, T .
HUMAN PATHOLOGY, 1997, 28 (09) :1010-1017
[10]   Pancreatic neoplasms with abundant mucus production: Emphasis on intraductal papillary-mucinous tumors and mucinous cystic tumors [J].
Fukushima, N ;
Mukai, K .
ADVANCES IN ANATOMIC PATHOLOGY, 1999, 6 (02) :65-77