Pancreatic mucinous cystic neoplasms with sarcomatous stroma: molecular evidence for monoclonal origin with subsequent divergence of the epithelial and sarcomatous components.
Neoplasms with mixed carcinomatous and sarcomatous growth patterns occur in many organs and tissues. The pathogenesis of these cancers is thought to be either the result of two independent neoplastic processes merging to form a single tumor, or a neoplasm of monoclonal origin that develops phenotypic diversity. To address this issue, we characterized molecular alterations in separately microdissected epithelial and sarcomatous areas in three cases of pancreatic mucinous cystic neoplasms with sarcomatous stroma. Using microsatellite markers for six chromosomal loci commonly deleted in infiltrating ductal adenocarcinomas of the pancreas, we found genetic alterations to be virtually identical between the sarcomatous and epithelial components of two of the three neoplasms. In the third neoplasm, we found allelic losses and retentions to be identical at five of the six chromosomal loci, but at a single locus, we noted allelic loss in the neoplastic epithelial component but not the sarcomatous component. The same neoplasms were also analyzed for activating point mutations in codon 12 of the K-ras gene by using mutant-enriched polymerase chain reaction and allele-specific oligonucleotide hybridization. A K-ras mutation was identified in the epithelial component of one of the three neoplasms (the same tumor with an additional allelic loss in the neoplastic epithelial cells), but the sarcomatous component of this tumor was wild-type at codon 12 of K-ras, as were both components of the other two neoplasms. Overall, these results suggest a monoclonal origin with subsequent divergence of the neoplastic epithelial and sarcomatous portions of these neoplasms.
van den Berg
W
W
Department of Pathology, the University of Amsterdam, The Netherlands.
Tascilar
M
M
Offerhaus
G J
GJ
Albores-Saavedra
J
J
Wenig
B M
BM
Hruban
R H
RH
Gabrielson
E
E
D002288:Adenocarcinoma, Mucinous / Q000235:genetics* / Q000473:pathology; D002296:Carcinosarcoma / Q000235:genetics* / Q000473:pathology; D002999:Clone Cells; D003560:Cysts / Q000473:pathology; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D019656:Loss of Heterozygosity; D018895:Microsatellite Repeats; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D017154:Stromal Cells / Q000473:pathology
D017931:DNA Primers; D004273:DNA, Neoplasm