Expression of C-kit in retinoblastoma: a potential therapeutic target.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Barry
Robert J
RJ
Department of Ophthalmology and Pathology, The McGill University Health Center & Henry C. Witelson Ocular Pathology Laboratory, Montreal, Canada.
de Moura
Letícia R
LR
Marshall
Jean-Claude
JC
Fernandes
Bruno F
BF
Orellana
Maria Eugenia
ME
Antecka
Emilia
E
Martins
Claudia
C
Burnier
Miguel N
MN
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002454:Cell Differentiation; D002648:Child; D002675:Child, Preschool; D002829:Choroid / Q000473:pathology; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D007223:Infant; D008297:Male; D009361:Neoplasm Invasiveness; D009900:Optic Nerve / Q000473:pathology; D011379:Prognosis; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D019572:Retinal Neoplasms / Q000378:metabolism* / Q000473:pathology; D012175:Retinoblastoma / Q000378:metabolism* / Q000473:pathology
D014408:Biomarkers, Tumor; D019009:Proto-Oncogene Proteins c-kit