Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas

E. Tamborini, P. Casieri, F. Miselli, M. Orsenigo, T. Negri, C. Piacenza, S. Stacchiotti, A. Gronchi, U. Pastorino, M. A. Pierotti, Silvana Pilotti

Research output: Contribution to journalArticle

28 Citations (Scopus)

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 languageEnglish
Pages (from-to)227-235
Number of pages9
JournalJournal of Pathology
Volume212
Issue number2
DOIs
Publication statusPublished - Jun 2007

Fingerprint

Tunica Intima
Receptor Protein-Tyrosine Kinases
Sarcoma
Platelet-Derived Growth Factor beta Receptor
Genes
Ligands
erbB-1 Genes
Gene Amplification
Immunoprecipitation
Cytogenetics
Neoplasms
Western Blotting
Immunohistochemistry
Phosphorylation
Mutation

Keywords

  • Gene amplification
  • Intimal sarcoma
  • Mural sarcoma
  • RTK activation profile

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Tamborini, E., Casieri, P., Miselli, F., Orsenigo, M., Negri, T., Piacenza, C., ... Pilotti, S. (2007). Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas. Journal of Pathology, 212(2), 227-235. https://doi.org/10.1002/path.2177

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 journalArticle

Tamborini, E, Casieri, P, Miselli, F, Orsenigo, M, Negri, T, Piacenza, C, Stacchiotti, S, Gronchi, A, Pastorino, U, Pierotti, MA & Pilotti, S 2007, 'Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas', Journal of Pathology, vol. 212, no. 2, pp. 227-235. https://doi.org/10.1002/path.2177
Tamborini, E. ; Casieri, P. ; Miselli, F. ; Orsenigo, M. ; Negri, T. ; Piacenza, C. ; Stacchiotti, S. ; Gronchi, A. ; Pastorino, U. ; Pierotti, M. A. ; Pilotti, Silvana. / Analysis of potential receptor tyrosine kinase targets in intimal and mural sarcomas. In: Journal of Pathology. 2007 ; Vol. 212, No. 2. pp. 227-235.
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