Pancreatic intraepithelial neoplasia and infiltrating adenocarcinoma: analysis of progression and recurrence by DPC4 immunohistochemical labeling.
Pancreatic intraepithelial neoplasia (PanIN) is thought to be a precursor lesion of infiltrating pancreatic ductal adenocarcinoma (IPA). DPC4 is a tumor-suppressor gene on chromosome 18q21.1 and is inactivated in approximately 55% of IPAs. Recently, immunohistochemical labeling using a monoclonal antibody to the Dpc4 protein has been shown to mirror DPC4 genetic status in invasive adenocarcinomas of the pancreas. In the present study, we examined the role of Dpc4 loss in neoplastic progression and recurrence. Two cases in which a PanIN clinically progressed to an invasive adenocarcinoma and a third of a patient with IPA of the head of the pancreas who later developed invasive adenocarcinoma in the tail of the pancreas were studied using Dpc4 immunolabeling. The first patient underwent pancreatic resection, which revealed PanIN-3 that lacked Dpc4 expression, and the patient developed an invasive pancreatic ductal carcinoma 10 years later that shared this loss of expression. The second patient had a pancreaticoduodenectomy for recurrent pancreatitis, and the resected pancreas contained PanIN-3 with intact Dpc4 expression. Seventeen months later, the patient developed an invasive adenocarcinoma of the distal pancreas that also had intact Dpc4 expression. In the third case, the patient underwent pancreaticoduodenectomy for an invasive ductal adenocarcinoma with negative margins. This carcinoma lacked Dpc4 expression. Three years later, resection of the pancreatic tail showed a second invasive adenocarcinoma. The cancer in the tail of the gland showed intact Dpc4 expression, suggesting it represented a second primary tumor, not a recurrence. We conclude that Dpc4 expression in PanIN can be predictive of Dpc4 expression in the subsequent invasive ductal adenocarcinoma. Additionally, Dpc4 expression can be used to differentiate recurrent or persistent adenocarcinoma from a second primary adenocarcinoma.
McCarthy
D M
DM
Departments of Pathology, Surgery, and Oncology, The Johns Hopkins Medical Institutions, Baltimore, MD, USA.
Brat
D J
DJ
Wilentz
R E
RE
Yeo
C J
CJ
Cameron
J L
JL
Kern
S E
SE
Hruban
R H
RH
D000230:Adenocarcinoma / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D000368:Aged; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D004268:DNA-Binding Proteins / Q000032:analysis*; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009364:Neoplasm Recurrence, Local; D010190:Pancreatic Neoplasms / Q000737:chemistry* / Q000473:pathology / Q000601:surgery; D051901:Smad4 Protein; D015534:Trans-Activators / Q000032:analysis*
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators