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 b e either the result of two independent neoplastic processes merging to form a single tumor, or a neoplasm of monoclonal origin that develops phenotypi c diversity. To address this issue, we characterized molecular alterations in separately microdissected epithelial and sarcomatous areas in three case s of pancreatic mucinous cystic neoplasms with sarcomatous stroma. Using mi crosatellite markers for six chromosomal loci commonly deleted in infiltrat ing ductal adenocarcinomas of the pancreas, we found genetic alterations to be virtually identical between the sarcomatous and epithelial components o f two of the three neoplasms. In the third neoplasm, we found allelic losse s and retentions to be identical at five of the six chromosomal loci, but a t a single locus, we noted allelic loss in the neoplastic epithelial compon ent but not the sarcomatous component. The same neoplasms were also analyze d for activating point mutations in codon 12 of the K-ras gene by using mut ant-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 lo ss in the neoplastic epithelial cells), but the sarcomatous component of th is 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 wi th subsequent divergence of the neoplastic epithelial and sarcomatous porti ons of these neoplasms.