SCIENTIFIC REPORT

Multidrug resistant proteins: P-glycoprotein and lung resistance protein expression in retinoblastoma

S Krishnakumar¹, K Mallikarjuna¹, N Desai², A Muthialu³, N Venkatesan¹, A Sundaram¹, V Khetan⁴ and M P Shanmugam⁴

¹ Department of Ocular Pathology, Vision Research Foundation, Chennai,Tamil Nadu, India
² Brown Medical School, Providence, RI, USA
³ Feinberg Northwestern School of Medicine, Chicago, IL, USA
⁴ Department Ocular Oncology, Medical and Vision Research Foundations, Sankara Nethralaya, Chennai, India

Correspondence to:
Correspondence to:
Dr Subramanian Krishnakumar
Department of Ocular Pathology, Vision Research Foundation, Sankara Nethralaya, 18 College Road, Chennai-600 006,Tamil Nadu, India; drkrishnakumar_2000{at}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.

Abbreviations: ATP, adenosine triphosphate; CSA, ciclosporin A; DLP, diode laser photocoagulation; EBRT, external beam radiation therapy; LRP, lung resistance protein; MDR, multidrug resistance proteins; P-gp, P-glycoprtein; TCC, transconjunctival cryopexy

Keywords: lung resistance protein; P-glycoprtein; multidrug resistance; retinoblastoma; immunohistochemistry; chemotherapy

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

• Balla, M. M. S., Vemuganti, G. K., Kannabiran, C., Honavar, S. G., Murthy, R. (2009). Phenotypic Characterization of Retinoblastoma for the Presence of Putative Cancer Stem-like Cell Markers by Flow Cytometry. IOVS 50: 1506-1514 [Abstract] [Full Text]  
• Rodriguez-Galindo, C., Wilson, M. W., Chantada, G., Fu, L., Qaddoumi, I., Antoneli, C., Leal-Leal, C., Sharma, T., Barnoya, M., Epelman, S., Pizzarello, L., Kane, J. R., Barfield, R., Merchant, T. E., Robison, L. L., Murphree, A. L., Chevez-Barrios, P., Dyer, M. A., O'Brien, J., Ribeiro, R. C., Hungerford, J., Helveston, E. M., Haik, B. G., Wilimas, J. (2008). Retinoblastoma: One World, One Vision. Pediatrics 122: e763-e770 [Abstract] [Full Text]  
• Stephan, H., Boeloeni, R., Eggert, A., Bornfeld, N., Schueler, A. (2008). Photodynamic Therapy in Retinoblastoma: Effects of Verteporfin on Retinoblastoma Cell Lines. IOVS 49: 3158-3163 [Abstract] [Full Text]  
• Mohan, A, Kandalam, M, Ramkumar, H L, Gopal, L, Krishnakumar, S (2006). Stem cell markers: ABCG2 and MCM2 expression in retinoblastoma. Br. J. Ophthalmol. 90: 889-893 [Abstract] [Full Text]  
• Wilson, M. W., Fraga, C. H., Fuller, C. E., Rodriguez-Galindo, C., Mancini, J., Hagedorn, N., Leggas, M. L., Stewart, C. F. (2006). Immunohistochemical detection of multidrug-resistant protein expression in retinoblastoma treated by primary enucleation.. IOVS 47: 1269-1273 [Abstract] [Full Text]  
• Dunkel, I J, Abramson, D H, Cordon-Cardo, C, Chantada, G L, de Davila, M T G, Fandino, A C (2005). P-glycoprotein expression in retinoblastoma. Br. J. Ophthalmol. 89: 784-784 [Full Text]  
• Eckstein, L. A., Van Quill, K. R., Bui, S. K., Uusitalo, M. S., O'Brien, J. M. (2005). Cyclosporin A Inhibits Calcineurin/Nuclear Factor of Activated T-Cells Signaling and Induces Apoptosis in Retinoblastoma Cells. IOVS 46: 782-790 [Abstract] [Full Text]  

eLetters:

Read all eLetters

p-glycoprotein expression in retinoblastoma

Ira J Dunkel, et al.

BJO Online, 8 Feb 2005 [Full text]