Abstract
Purpose: :
Chemotherapy plays an important role in the management of retinoblastoma (RB). Earlier we showed that RB express the Multidrug Resistant Proteins P–glycoprotein (P–gp) and Lung Resistant Protein (LRP) even prior chemotherapy, but we were not able to correlate the expression of these proteins with clinical outcome. Hence, there could be other mechanisms that contribute to drug resistance. Studies by Schenk et al. have shown that Serine/arginine–rich protein–specific kinase 1 (SRPK1) is a novel cisplatin sensitive gene whose inactivation correlates with cellular resistance to cisplatin. The present study was aimed at examining the expression of SRPK1 in RB.
Methods: :
SRPK1 expression in RB was studied by immunohistochemistry using a monoclonal antibody (G211–637, BD Biosciences, Pharmingen, USA) in the Y79 retinoblastoma cell line and in 3 groups of tumors – Group 1: Tumors (N=33) from patients not subjected to preoperative or postoperative chemotherapy, Group 2: Tumors (N=17) from patients subjected to postoperative chemotherapy and Group 3: Tumors (N=13) from patients subjected to preoperative chemotherapy only. Immunoreactivity was graded as positive, reduced and negative for SRPK1. SRPK1 expression was correlated with clinical outcome, tumor grade as adapted to the International Intraocular Retinoblastoma Classification (IIRC), laterality and differentiation of tumors.
Results: :
The Y79 cell line was positive for SRPK1. Among the 63 tumors, 62 tumors were in advanced categories D and E (IIRC) and SRPK1 was reduced in 45 (71%) tumors. Among 50 tumors of Groups 1 and 2, 35 (70%) showed reduced SRPK1 expression. In 13 tumors of Group 3, SRPK1 was reduced in 10 (77%) tumors. Among 8 patients (Group 2) who developed orbital reccurence and/or metastasis, SRPK1 was reduced in 6 (75%) tumors. Among 9 patients (Group 2) who responded well with postoperative chemotherapy, SRPK1 was positive in 5 (55.5%) tumors. There was no correlation of SRPK1 expression with differentiation or laterality of tumors.
Conclusions: :
SRPK1 positivity of Y79 Rb cell line is in accordance with prior studies that demonstrate that it is cisplatin sensitive. A majority of retinoblastomas were in the advanced stage and expressed reduced SRPK1 even prior to chemotherapy. Further studies are required to confirm our initial findings and to examine it’s relation with drug resistance in retinoblastoma.
Keywords: retinoblastoma • tumors