Fluorescence in situ hybridization analysis and immunophenotyping of c-Kit/PDGFRA and Bcl-2 expression in gastrointestinal stromal tumors

Marta Orsenigo, Silvia Brich, Carla Riva, Elena Conca, Rossella Bertulli, Palma Dileo, Alessandro Gronchi, Paolo G. Casali, Marco A. Pierotti, Elena Tamborini, Silvana Pilotti

Research output: Contribution to journalArticlepeer-review

Abstract

OBJECTIVE: To investigate c-Kit/PDGFRA genomic alterations, KIT-PDGFRA coexpression in gastrointestinal stromal tumors (GISTs) and the role of Bcl-2. STUDY DESIGN: We analyzed 70 primary tumors, 6 recurrences, 4 metastases and 1 recurrence plus metastasis, all molecularly characterized. Alterations in gene copy number were detected by fluorescence in situ hybridization (FISH) and expression of KIT, PDGFRA and Bcl-2 by immunohistochemistry. RESULTS: c-Kit/PDGFRA gene alterations affected 38% of all cases and 39% of primary tumors, with major changes accounting for 15% in both all the cases and primary tumors. Cytoplasmic KIT/PDGFRA coexpression was present in 96.5% of the c-Kit-mutated cases, 100% of the wt c-Kit/PDGFRA cases and 66.6% of the PDGFRA-mutated cases. Bcl-2 immunoreactivity was present in 70% of cases, with expression levels of +++ in 29%, ++ in 38% and + in 33%. CONCLUSION: FISH confirmed cytogenetic alterations in about 40% of primary GISTs at the onset. The high rate of c-Kit/PDGFRA coexpression suggests that both receptors are involved in oncogenicity and may affect imatinib efficacy. The assumption that Bcl-2 expression is supported by the KIT pathway and that its imatinib-mediated down-regulation contributes to autophagic cell death, although attractive, needs to be further confirmed.

Original languageEnglish
Pages (from-to)225-233
Number of pages9
JournalAnalytical and Quantitative Cytology and Histology
Volume32
Issue number4
Publication statusPublished - Aug 2010

Keywords

  • Bcl-2
  • c-Kit/PDGFRA gene alterations
  • Gastrointestinal stromal tumors
  • Immunohistochemistry
  • Molecular analysis

ASJC Scopus subject areas

  • Anatomy
  • Histology

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