TY - JOUR
T1 - Pancreatic mucinous cystic neoplasms with sarcomatous stroma
T2 - Molecular evidence for monoclonal origin with subsequent divergence of the epithelial and sarcomatous components
AU - Van Den Berg, Wiebren
AU - Tascilar, Metin
AU - Offerhaus, G. Johan A.
AU - Albores-Saavedra, Jorge
AU - Wenig, Bruce M.
AU - Hruban, Ralph H.
AU - Gabrielson, Edward
N1 - Funding Information:
Copyright © 2000 by The United States and Canadian Academy of Pathology, Inc. VOL. 13, NO. 1, P. 86, 2000 Printed in the U.S.A. Supported in part by National Institutes of Health Grant P50CA-62924 and NOW Grant 950–10-625. Address reprint requests to: Dr. Edward Gabrielson, Johns Hopkins Bay-view Medical Center, 4940 Eastern Avenue, Baltimore, MD 21224.
PY - 2000/1
Y1 - 2000/1
N2 - 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.
AB - 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.
KW - Carcinosarcoma
KW - K-ras
KW - Loss of heterozygosity
KW - Neoplasms
KW - Pancreas
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U2 - 10.1038/modpathol.3880013
DO - 10.1038/modpathol.3880013
M3 - Article
C2 - 10658914
AN - SCOPUS:0033980242
SN - 0893-3952
VL - 13
SP - 86
EP - 91
JO - Modern Pathology
JF - Modern Pathology
IS - 1
ER -