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Multidrug resistant proteins: P-glycoprotein and lung resistance protein expression in retinoblastoma
S Krishnakumar1, K Mallikarjuna, N Desai
1Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006,Tamil Nadu, India. drkrishnakumar_2000@yahoo.com
Background/Aim:
Retinoblastoma is the commonest primary intraocular tumour in children. Chemotherapy now plays a big part in the treatment of these tumours. There is not much information about the role of the multidrug resistance proteins (MDR)-P-glycoprotein (P-gp) and vault protein lung resistance protein (LRP)-in retinoblastoma. The authors investigated the expression of P-gp and LRP in retinoblastoma and correlated them clinicopathologically.
Methods:
Among 60 retinoblastomas, 40 tumours were not subjected to preoperative or postoperative chemotherapy and 20 tumours were subjected to postoperative chemotherapy. In this cohort 27 tumours had no invasion and 33 tumours had invasion of choroid, optic nerve, and orbit. P-gp and LRP expression were studied by immunohistochemistry. Immunoanalysis was done semiquantitatively.
Results:
Among the 60 tumours P-gp was expressed in 23 (38%) tumours and LRP was expressed in 35 (58%). P-gp was expressed in 11/27 (40%) tumours with no invasion and in 12/33 (36%) tumours with invasion. LRP was expressed in 15/27 (55%) tumours with no invasion and in 20/33 (60%) tumours with invasion. Both P-gp and LRP were negative in three tumours with invasion, which had later developed bone marrow metastasis. There was no correlation between P-gp and LRP expression with invasion, differentiation and laterality of the tumours and response to treatment.
Conclusion:
Retinoblastoma expresses P-gp and LRP intrinsically before chemotherapy and none of these proteins predicted the response to chemotherapy. Thus, further studies are needed to understand the significance of the expression of the P-gp and LRP proteins in retinoblastoma.
Insights
Retinoblastoma tumors express multidrug resistance proteins P-glycoprotein (P-gp) and lung resistance protein (LRP) intrinsically. However, their expression does not predict chemotherapy response in these pediatric eye cancers.
Area of Science:
- Ophthalmology
- Pediatric Oncology
- Molecular Biology
Background:
- Retinoblastoma is a common childhood intraocular tumor.
- Chemotherapy is a key treatment modality for retinoblastoma.
- The role of multidrug resistance proteins, P-glycoprotein (P-gp) and lung resistance protein (LRP), in retinoblastoma is not well understood.
Purpose of the Study:
- To investigate the expression of P-gp and LRP in retinoblastoma.
- To correlate P-gp and LRP expression with clinicopathological features of retinoblastoma.
- To assess the predictive value of P-gp and LRP expression for chemotherapy response.
Main Methods:
- Immunohistochemistry was used to study P-gp and LRP expression in 60 retinoblastoma samples.
- Samples included tumors with and without preoperative/postoperative chemotherapy, and with varying degrees of invasion.
- Immunoanalysis was performed semiquantitatively.
Main Results:
- P-gp was expressed in 38% of tumors, and LRP in 58%.
- Expression levels of P-gp and LRP did not correlate with tumor invasion, differentiation, laterality, or response to chemotherapy.
- P-gp and LRP were negative in three invasive tumors that later developed bone marrow metastasis.
Conclusions:
- Retinoblastoma intrinsically expresses P-gp and LRP prior to chemotherapy.
- Neither P-gp nor LRP expression predicted chemotherapy response in this study.
- Further research is required to elucidate the clinical significance of P-gp and LRP expression in retinoblastoma.
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