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

Abstract

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.

Figure 1

P-glycoprotein (P-gp) expression in retinoblastoma. (A) Microphotograph showing P-gp in the membrane of the tumour cells (in >10% of the tumour cells with bright intensity) in retinoblastoma with no invasion (DAB with haematoxylin and eosin counterstain, ×200). (B) Microphotograph showing the P-gp in the membrane of the tumour cells (in >10% of the tumour cells with dull intensity) in a child who had orbital recurrence (DAB with haematoxylin and eosin counterstain, ×100). (C) Microphotograph showing the P-gp in the membrane of the tumour cells (in 30–40% of the tumour cells with dull intensity) in retinoblastoma with no invasion (DAB with haematoxylin and eosin counterstain, ×100).

Figure 2

Lung resistance protein (LRP) expression in retinoblastoma. (A) Microphotograph showing the LRP in the cytoplasm of the tumour cells (>10% cells stained with bright intensity) in retinoblastoma with no invasion (DAB with haematoxylin and eosin counterstain, ×200). Inset shows the lower magnification of the same). (B) Microphotograph showing the LRP (in >10% of the tumour cells with dull intensity) in retinoblastoma in with invasion (DAB with haematoxylin and eosin counterstain, ×100). (C) Microphotograph showing the LRP (in >10% of the tumour cells with bright intensity) in the pretreatment tumour sample in a child with no invasion. (DAB with haematoxylin and eosin counterstain, ×100).