Dpc4 is expressed in virtually all primary and metastatic pancreatic endocrine carcinomas.
DPC4/Smad4 is inactivated in about 50% of pancreatic ductal cancers. It has been recently reported that this gene is also inactivated in neoplasms arising from pancreatic islet cells, a phenomenon suggested to be related to similar progressions of malignancy found in common ductal cancers. To evaluate this possibility, we analysed 20 metastases of pancreatic endocrine carcinomas and their corresponding primary lesion for inactivation of DPC4 using immunohistochemical staining. In fact, immunohistochemical labelling has been shown to correlate with DPC4 gene status with high sensitivity and specificity. The cancers included 18 nonfunctioning tumours, one gastrinoma and one ViPoma all with liver, nodal and/or adrenal metastases. Seventeen were well-differentiated and three poorly differentiated endocrine carcinomas. Dpc4 expression was absent in only one primary well-differentiated endocrine cancer and its liver metastasis, while all the remaining 19 primary tumours and their metastases stained positive for the protein. All positively staining cases showed diffuse cytoplasmic and nuclear staining in virtually all neoplastic cells. Our data suggest that DPC4 is only rarely involved in pancreatic endocrine tumourigenesis and give further weight to the hypothesis that tumours arising from pancreatic exocrine and endocrine epithelia are genetically distinct.
Scarpa
Aldo
A
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
Orlandini
Simonetta
S
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
Moore
Patrick S
PS
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
Lemoine
Nicholas R
NR
ICRF Molecular Oncology Unit, Department of Cancer Medicine, Imperial College School of Medicine, London, UK, UK.
Beghelli
Stefania
S
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
Baron
Antonella
A
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
Falconi
Massimo
M
Department of Surgery, University of Verona, Italy, Italy.
Zamboni
Giuseppe
G
Dipartimento di Patologia, Sezione di Anatomia Patologica, Università di Verona, Strada Le Grazie, 37134 Verona, Italy, Italy.
D000328:Adult; D000368:Aged; D018273:Carcinoma, Islet Cell / Q000378:metabolism* / Q000556:secondary; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000378:metabolism / Q000556:secondary; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D051901:Smad4 Protein; D015534:Trans-Activators / Q000096:biosynthesis*; D016212:Transforming Growth Factor beta / Q000096:biosynthesis*; D014407:Tumor Cells, Cultured
D004268:DNA-Binding Proteins; C497796:SMAD4 protein, human; D051901:Smad4 Protein; D015534:Trans-Activators; D016212:Transforming Growth Factor beta