Abstract
Purpose:
The aim of this study was to: 1/ Determine the immunoexpression of PDGFR-α, PDGFR-β and c-Abl, known targets of imatinib mesylate (Gleevec), in human retinoblastoma specimens. 2/ Determine if the expression of PDGFR-α, PDGFR-β and c-Abl in retinoblastoma correlate with histopathological prognostic factors (optic nerve invasion and choroid invasion).
Methods:
Sixty-one paraffin-embedded retinoblastomas were collected from the archives of the Henry C Witelson Ocular Pathology Laboratory. PDGFR-α, -β and c-Abl immunostaining was performed 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. Optic nerve (ON) invasion was considered positive when tumor cells could be identified beyond the lamina cribrosa, and choroidal invasion was considered positive when tumor cells were seen to infiltrate through Bruch's membrane. The Fisher Exact Test was used to assess whether the immunostainining expression differed with optic nerve or choroid invasion. Statistical significance was assumed if the p value was less than 0.05.
Results:
Overall, c-Abl expression was identified in 50 of 61 specimens (81.97%), PDGFR-α was identified in 20 of 60 specimens (33.33%) and PDGFR-β expression was identified in 57 of 61 specimens (93.44%). The only correlation of statistical significance was that PDGFR-β expression was negatively correlated with optic nerve involvement (P=0.034).
Conclusions:
This paper provides convincing evidence that retinoblastoma (Rb) is a cancer that expresses the receptor tyrosine kinases (RTKs) PDGFR-α, PDGFR-β and c-Abl. The Henry C Witelson laboratory has shown a pharmacological effect of imatinib mesylate (Gleevec) on Rb cells in vitro (manuscript in review). Additional in vitro studies should be done to decipher if the expression of the RTKs in question are relevant to the pharmacological action of Gleevec on Rb cells, as this drug is known to act through other pathways, not solely RTKs. (Additionally, PDGFR-β expression is negatively correlated with a poor histopathological prognosis).
Keywords: 703 retinoblastoma •
554 immunohistochemistry •
744 tumors