Expression of C-kit in retinoblastoma: a potential therapeutic target
Robert J. BarryLetícia Rielo de MouraJ.–C.A. MarshallBruno F. FernandesMaría Eugenia OrellanaE. AnteckaCláudio MartinsMiguel N. Burnier
6
Citation
25
Reference
10
Related Paper
Citation Trend
Abstract:
C-kit is a transmembrane tyrosine kinase protein thought to play an important role in tumourigenesis. With the development of the compound imatinib mesylate, which specifically inhibits tyrosine kinase receptors, C-kit has emerged as a potential therapeutic target. This study aims to determine the immunoexpression of C-kit in retinoblastoma and correlate this expression with histopathological prognostic features.Eighty-four paraffin-embedded retinoblastomas were collected from the Henry C Witelson Ocular Pathology Registry. C-kit immunostaining was used according to the protocol provided by Ventana Medical System Inc., Arizona. Immunoreactivity was correlated with the presence or absence of invasion into the choroid and optic nerve and the degree of tumour differentiation. Odds ratios were calculated to quantify differences in C-kit expression between tumours with different patterns of invasion and differentiation.Twenty-one slides (25%) were excluded from analysis because of the presence of extensive tissue necrosis or the absence of sufficient optic nerve tissue for analysis. Overall, C-kit expression was identified in 33/63 specimens analysed (52.38%). Two of the 13 tumours without choroidal or optic nerve invasion (15.4%) were positive for C-kit. C-kit expression was seen in 31 of the 50 tumours with extraretinal invasion (62%, p<0.01), 26 of 44 specimens with choroidal involvement (59.9%, p<0.2), and 20 of the 29 with optic nerve involvement (68.96%, p<0.02). Fourteen of 25 moderate or well-differentiated specimens (56%) and 19 of 38 undifferentiated specimens (50%) displayed positivity for C-kit (p>0.5).More than half the retinoblastomas in this study expressed C-kit. The expression of C-kit strongly correlated with histopathological features of a worse prognosis including optic nerve and choroidal invasion.Keywords:
Retinoblastoma
Immunostaining
Proto-Oncogene Proteins c-kit
Imatinib Mesylate
Choroid
Tissue microarray
Objective To detect Bag-1 expression in retinoblastoma and normal tissue with tissue microarray and to discuss it's clinical significance.Methods The experiment was done in the Laboratory of the Fourth Military Medical University of Chinese PLA between June and August 2005.Tissue microarray of retinoblastoma and normal retina tissues were used to determine the expression of Bag-1 with immunohistochemical S-A system.Results Bag-1 was detected strong expression in the nucleus and cytoplasm in the cancer tissue,while it was hardly seen in the normal retinal cells.There were significant difference of positive rates of Bag-1 expression between the cancer tissue and the normal tissues(P0.05).Conclusion There is an over expression of Bag-1 in retinoblastoma,suggesting that Bag-1 may be related to retinoblastoma.
Retinoblastoma
Tissue microarray
Cite
Citations (0)
Imatinib Mesylate
Proto-Oncogene Proteins c-kit
Mesylate
Cite
Citations (249)
Retinoblastoma
Cite
Citations (170)
Objective To detect the expression of Hsp70 in tissue microarray of retinoblastoma and normal retina,to evaluate it's clinical significance.Methods Tissue microarray of retinoblastoma and normal retina tissues were analyzed by S-A immunohistochemical staining for Hsp70 expression.Results Hsp70 was over expressed in cytoplasm in cancer tissue(13/16),while it was hardly seen in normal retinal tissues(1/5).There were significant difference in the positive rate of Hsp70 between the cancer tissue and the normal retinal tissues(P=0025 40.05).Conclusion There is over expression of Hsp70 in retinoblastoma,which suggests that it may be related to the development of retinoblastoma.
Retinoblastoma
Tissue microarray
Cite
Citations (0)
Imatinib Mesylate
Proto-Oncogene Proteins c-kit
Cite
Citations (25)
Objective To detect p53 and Bag-1 expression in retinoblastoma cells by tissue microarray and to evaluate their clinical significance.Methods Tissue microarray of retinoblastoma and normal retinal tissues were used to determine the expression of p53 and Bag-1 with S-A system.Results p53 were highly expressed in retinoblastoma tissue(13/16),while not expressed in normal retinal tissue(0/5).There were significant difference in the positive rate between the cancer tissue and the normal tissue(P=0.002 750.05).Bag-1 were highly expressed in retinoblastoma tissue(14/16),while slightly expressed in normal retinal tissue(1/5).There were significant difference in the positive rate between the cancer tissue and the normal tissue(P=0.011 40.05).Conclusion There are over-expression of p53 and Bag-1 in retinoblastoma,which suggests that p53 and Bag-1 may be involved in the development of retinoblastoma.
Retinoblastoma
Tissue microarray
Cite
Citations (0)
Human retinoblastoma is caused by mutational inactivation of the retinoblastoma suppressor gene (RB). We have examined intraocular tumorigenicity of retinoblastoma cells in which RB expression was achieved by retroviral transduction. Retinoblastoma cells were injected into the anterior chambers of severe combined immunodeficient mouse eyes, and tumorigenicity was assessed. RB-expressing retinoblastoma cells usually failed to form progressive tumors in the anterior chamber, whereas the parental, RB-negative line, WERI-Rb27, was rapidly tumorigenic. These results support the hypothesis that inactivation of the RB gene is critical for the growth of retinoblastoma tumors. The potential use of RB reconstitution for treating human retinoblastoma is suggested by our finding that intraocular tumor growth can be suppressed by RB expression.
Retinoblastoma
Retinoblastoma protein
Cite
Citations (41)
Imatinib Mesylate
Stromal tumor
Mesylate
CD117
Proto-Oncogene Proteins c-kit
Cite
Citations (73)
Imatinib Mesylate
Mesylate
Proto-Oncogene Proteins c-kit
ABL
Cite
Citations (46)
Retinoblastoma
Eye neoplasm
Cite
Citations (2)