ABSTRACT
PURPOSE: We set out to evaluate alterations of the therapeutic target genes KIT (CD 117), EGFR, and HER-2 in human retinoblastoma. METHODS: Ninety-five formalin-fixed, paraffin-embedded retinoblastomas were brought into a tissue microarray (TMA) format. Immunohistochemistry was performed to analyze the expression of CD117, EGFR, and HER-2. Fluorescence in situ hybridization (FISH) was utilized for detection of EGFR amplifications. Three tumors with strong CD117 positivity were sequenced for KIT exon 11 mutations. RESULTS: Detectable CD117 expression was seen in 19% of all interpretable cases. Sequence analysis of the three tumors with the strongest CD117 expression revealed no mutations. EGFR was positive in 14% of all cases. No EGFR amplification was observed by FISH, however. All tumors were negative for HER-2 expression. CONCLUSIONS: Our data suggest that selected cases of retinoblastoma may be candidates for anti-EGFR and imatinib mesylate (STI571) therapy.
Subject(s)
ErbB Receptors/genetics , Gene Amplification/physiology , Gene Expression Regulation, Neoplastic/physiology , Genes, erbB-2/genetics , Proto-Oncogene Proteins c-kit/genetics , Retinal Neoplasms/genetics , Retinoblastoma/genetics , Adolescent , Adult , Child , Child, Preschool , Female , Humans , Immunoenzyme Techniques , In Situ Hybridization, Fluorescence , MaleABSTRACT
We aimed to immunohistochemically examine the expression of KIT (CD 117) in human posterior uveal melanoma and to analyze KIT-positive tumors for gene mutations. Brought into a tissue microarray (TMA) format were 101 formalin-fixed, paraffin-embedded posterior uveal melanomas. Immunohistochemistry was performed using the polyclonal anti-CD117 antibody from Dako (A4502). In ten selected KIT-positive tumors, exons 2, 8, 9, 11, 13 and 17 were sequenced. Of the 101 cases, 89 (88%) could be evaluated on the TMAs. Immunohistochemistry for CD 117 was weakly positive in 5 cases (6%), moderately positive in 10 cases (12%) and strongly positive in 57 cases (69%). No KIT mutations were detected in the analyzed exons. In conclusion, human posterior uveal melanoma frequently expresses CD117 at high levels. Although KIT mutations could not be found, it appears justified to investigate the utility of imatinib mesylate in the treatment of these patients.
