Fluorescence in situ hybridization analysis and immunophenotyping of c-Kit/PDGFRA and Bcl-2 expression in gastrointestinal stromal tumors
| Autor: | Marta, Orsenigo, Silvia, Brich, Carla, Riva, Elena, Conca, Rossella, Bertulli, Palma, Dileo, Alessandro, Gronchi, Paolo G, Casali, Marco A, Pierotti, Elena, Tamborini, Silvana, Pilotti |
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| Rok vydání: | 2011 |
| Předmět: |
Adult
Male Receptor Platelet-Derived Growth Factor alpha Gastrointestinal Stromal Tumors Biopsy Drug Resistance Gene Dosage Antineoplastic Agents Middle Aged Piperazines Immunophenotyping Gene Expression Regulation Neoplastic Proto-Oncogene Proteins c-kit Pyrimidines Proto-Oncogene Proteins c-bcl-2 Benzamides Imatinib Mesylate Humans Female In Situ Hybridization Fluorescence Aged |
| Zdroj: | Analytical and quantitative cytology and histology. 32(4) |
| Popis: | To investigate c-Kit/PDGFRA genomic alterations, KIT-PDGFRA coexpression in gastrointestinal stromal tumors (GISTs) and the role of Bcl-2.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.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%.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. |
| Databáze: | OpenAIRE |
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