PMID- 21434524
OWN - NLM
STAT- MEDLINE
DCOM- 20110418
LR  - 20161020
IS  - 0884-6812 (Linking)
VI  - 32
IP  - 4
DP  - 2010 Aug
TI  - Fluorescence in situ hybridization analysis and immunophenotyping of c-Kit/PDGFRA 
      and Bcl-2 expression in gastrointestinal stromal tumors.
PG  - 225-33
AB  - 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.
FAU - Orsenigo, Marta
AU  - Orsenigo M
AD  - Unit of Experimental Molecular Pathology, Department of Pathology, Fondazione 
      Istituto di Ricerca e di Cura a Carattere Scientifico (IRCCS), Istituto Nazionale 
      dei Tumori, Milan, Italy.
FAU - Brich, Silvia
AU  - Brich S
FAU - Riva, Carla
AU  - Riva C
FAU - Conca, Elena
AU  - Conca E
FAU - Bertulli, Rossella
AU  - Bertulli R
FAU - Dileo, Palma
AU  - Dileo P
FAU - Gronchi, Alessandro
AU  - Gronchi A
FAU - Casali, Paolo G
AU  - Casali PG
FAU - Pierotti, Marco A
AU  - Pierotti MA
FAU - Tamborini, Elena
AU  - Tamborini E
FAU - Pilotti, Silvana
AU  - Pilotti S
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Anal Quant Cytol Histol
JT  - Analytical and quantitative cytology and histology
JID - 8506819
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Benzamides)
RN  - 0 (Piperazines)
RN  - 0 (Proto-Oncogene Proteins c-bcl-2)
RN  - 0 (Pyrimidines)
RN  - 8A1O1M485B (Imatinib Mesylate)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-kit)
RN  - EC 2.7.10.1 (Receptor, Platelet-Derived Growth Factor alpha)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Antineoplastic Agents/therapeutic use
MH  - Benzamides
MH  - Biopsy
MH  - Drug Resistance/genetics
MH  - Female
MH  - Gastrointestinal Stromal Tumors/drug therapy/*genetics/pathology
MH  - Gene Dosage
MH  - *Gene Expression Regulation, Neoplastic
MH  - Humans
MH  - Imatinib Mesylate
MH  - Immunophenotyping
MH  - In Situ Hybridization, Fluorescence
MH  - Male
MH  - Middle Aged
MH  - Piperazines/therapeutic use
MH  - Proto-Oncogene Proteins c-bcl-2/*genetics/metabolism
MH  - Proto-Oncogene Proteins c-kit/*genetics/metabolism
MH  - Pyrimidines/therapeutic use
MH  - Receptor, Platelet-Derived Growth Factor alpha/*genetics/metabolism
EDAT- 2011/03/26 06:00
MHDA- 2011/04/19 06:00
CRDT- 2011/03/26 06:00
PHST- 2011/03/26 06:00 [entrez]
PHST- 2011/03/26 06:00 [pubmed]
PHST- 2011/04/19 06:00 [medline]
PST - ppublish
SO  - Anal Quant Cytol Histol. 2010 Aug;32(4):225-33.