Abstract
Primary sarcomas of the great vessels are very rare, neoplasms and only a few cases have been reported. They are divided into the two broad categories of intimal or luminal and mural sarcomas. We analysed eight advanced high-grade sarcomas originating from major vessels (seven intimal and one mural sarcoma) by means of immunohistochemistry and FISH analysis for PDGFRA, PDGFRB, EGFR and KIT receptor tyrosine kinases (RTKs), together with immunoprecipitation/western blotting, sequencing of the corresponding genes, and the search for cognate ligands. The intimal sarcomas showed a wide spectrum of morphologies and immunophenotypes, whereas the mural sarcoma had common leiomyosarcomatous features. Regardless of their category, all of the cases had a PDGFRA-deregulated cytogenetic profile mainly consisting of an amplification cluster; five were also polysomic for PDGFPB, whereas three showed disomy. Six cases had a deregulated EGFR gene, and c-Kit gene status was similar to that of PDGFRA. In one case, biochemical analysis revealed the presence of activated and highly expressed PDGFRA, PDGFRB and EGFR, whereas KIT was expressed at reference level. Sequencing of the corresponding genes revealed no activating mutations in any of the analysed receptors. The cognate ligands were detected in all cases. In predictive terms, the evidence of gene amplification/high polysomy of several RTKs, together with PDGFRA, PDGFRB and EGFR expression and phosphorylation, suggests that these tumours may be sensitive to RTK-inhibiting treatments.
| Original language | English |
|---|---|
| Pages (from-to) | 227-235 |
| Number of pages | 9 |
| Journal | Journal of Pathology |
| Volume | 212 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Jun 2007 |
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Keywords
- Gene amplification
- Intimal sarcoma
- Mural sarcoma
- RTK activation profile
ASJC Scopus subject areas
- Pathology and Forensic Medicine
Cite this
Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas. / Tamborini, E.; Casieri, P.; Miselli, F.; Orsenigo, M.; Negri, T.; Piacenza, C.; Stacchiotti, S.; Gronchi, A.; Pastorino, U.; Pierotti, M. A.; Pilotti, Silvana.
In: Journal of Pathology, Vol. 212, No. 2, 06.2007, p. 227-235.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas
AU - Tamborini, E.
AU - Casieri, P.
AU - Miselli, F.
AU - Orsenigo, M.
AU - Negri, T.
AU - Piacenza, C.
AU - Stacchiotti, S.
AU - Gronchi, A.
AU - Pastorino, U.
AU - Pierotti, M. A.
AU - Pilotti, Silvana
PY - 2007/6
Y1 - 2007/6
N2 - Primary sarcomas of the great vessels are very rare, neoplasms and only a few cases have been reported. They are divided into the two broad categories of intimal or luminal and mural sarcomas. We analysed eight advanced high-grade sarcomas originating from major vessels (seven intimal and one mural sarcoma) by means of immunohistochemistry and FISH analysis for PDGFRA, PDGFRB, EGFR and KIT receptor tyrosine kinases (RTKs), together with immunoprecipitation/western blotting, sequencing of the corresponding genes, and the search for cognate ligands. The intimal sarcomas showed a wide spectrum of morphologies and immunophenotypes, whereas the mural sarcoma had common leiomyosarcomatous features. Regardless of their category, all of the cases had a PDGFRA-deregulated cytogenetic profile mainly consisting of an amplification cluster; five were also polysomic for PDGFPB, whereas three showed disomy. Six cases had a deregulated EGFR gene, and c-Kit gene status was similar to that of PDGFRA. In one case, biochemical analysis revealed the presence of activated and highly expressed PDGFRA, PDGFRB and EGFR, whereas KIT was expressed at reference level. Sequencing of the corresponding genes revealed no activating mutations in any of the analysed receptors. The cognate ligands were detected in all cases. In predictive terms, the evidence of gene amplification/high polysomy of several RTKs, together with PDGFRA, PDGFRB and EGFR expression and phosphorylation, suggests that these tumours may be sensitive to RTK-inhibiting treatments.
AB - Primary sarcomas of the great vessels are very rare, neoplasms and only a few cases have been reported. They are divided into the two broad categories of intimal or luminal and mural sarcomas. We analysed eight advanced high-grade sarcomas originating from major vessels (seven intimal and one mural sarcoma) by means of immunohistochemistry and FISH analysis for PDGFRA, PDGFRB, EGFR and KIT receptor tyrosine kinases (RTKs), together with immunoprecipitation/western blotting, sequencing of the corresponding genes, and the search for cognate ligands. The intimal sarcomas showed a wide spectrum of morphologies and immunophenotypes, whereas the mural sarcoma had common leiomyosarcomatous features. Regardless of their category, all of the cases had a PDGFRA-deregulated cytogenetic profile mainly consisting of an amplification cluster; five were also polysomic for PDGFPB, whereas three showed disomy. Six cases had a deregulated EGFR gene, and c-Kit gene status was similar to that of PDGFRA. In one case, biochemical analysis revealed the presence of activated and highly expressed PDGFRA, PDGFRB and EGFR, whereas KIT was expressed at reference level. Sequencing of the corresponding genes revealed no activating mutations in any of the analysed receptors. The cognate ligands were detected in all cases. In predictive terms, the evidence of gene amplification/high polysomy of several RTKs, together with PDGFRA, PDGFRB and EGFR expression and phosphorylation, suggests that these tumours may be sensitive to RTK-inhibiting treatments.
KW - Gene amplification
KW - Intimal sarcoma
KW - Mural sarcoma
KW - RTK activation profile
UR - http://www.scopus.com/inward/record.url?scp=34249848684&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34249848684&partnerID=8YFLogxK
U2 - 10.1002/path.2177
DO - 10.1002/path.2177
M3 - Article
C2 - 17471466
AN - SCOPUS:34249848684
VL - 212
SP - 227
EP - 235
JO - Journal of Pathology
JF - Journal of Pathology
SN - 0022-3417
IS - 2
ER -