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 Table of Contents    
LETTER TO THE EDITOR
Year : 2012  |  Volume : 5  |  Issue : 2  |  Page : 136-137  

An immunohistochemical analysis of P-glycoprotein in retinoblastoma


1 Oculoplastic and Pediatric Ophthalmology Services, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
2 Department of Ocular Biochemistry, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India
3 Department of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi, India

Date of Web Publication4-Aug-2012

Correspondence Address:
Seema Kashyap
Department of Ocular Pathology, Dr. Rajendra Prasad Centre for Ophthalmic Sciences, All India Institute of Medical Sciences, New Delhi
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0974-620X.99386

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How to cite this article:
Sethi S, Saxena P, Kashyap S, Pushker N, Kaur J, Ghose S. An immunohistochemical analysis of P-glycoprotein in retinoblastoma. Oman J Ophthalmol 2012;5:136-7

How to cite this URL:
Sethi S, Saxena P, Kashyap S, Pushker N, Kaur J, Ghose S. An immunohistochemical analysis of P-glycoprotein in retinoblastoma. Oman J Ophthalmol [serial online] 2012 [cited 2020 Feb 20];5:136-7. Available from: http://www.ojoonline.org/text.asp?2012/5/2/136/99386

Sir,

Retinoblastoma is the most frequent primary intraocular malignancy in children. [1] Even with the use of multidrug chemotherapy regimens, drug resistance is a major problem while managing this vulnerable group of patients. Multidrug resistance (MDR), associated with expression of P-glycoprotein (P-gp), is one of the most known mechanisms of chemoresistance. [2],[3] P-gp is a 170-kDa plasma membrane glycoprotein, which is known to cause an increased efflux of cytotoxic drugs from the cell. In other systemic malignancies, overexpression of P-gp has been associated with chemoresistance and poor prognosis. [2] We analyzed P-gp expression in retinoblastoma specimens enucleated either primarily or after neoadjuvant chemotherapy by immunohistochemistry and correlated this with the histopathological findings.

All eyes enucleated over a 1-year period from January 2010 to December 2010; enucleated either as a primary treatment (group I) or after three to five cycles of standard regimen vincristine, etoposide, and carboplatin (group II) were included in the study. Formalin fixed, paraffin-embedded sections from the enucleated sections were stained with hematoxylin and eosin for studying histopathological features (tumor differentiation and high-risk features). P-gp immunostaining was done and analyzed semiquantitatively as negative, low, or high expression [Figure 1]. Fischer's exact and chi-square tests were used for statistical analysis. Statistical significance was set at a P-value of less than 0.05.

There were a total of 49 eyes, 37 in group I (mean age 2.48 ± 1.27 years) and 12 in group II (mean age 3.21 ± 1.34); histopathological findings of both the groups are summarized in [Table 1]. In group I, there were 27% (10 of 37) eyes with positive P-gp expression, of which 5.4% (2 of 37) were high expressions. In group II, among 58.3% (7 of 12) positive cases, P-gp was highly expressed in 41.7% (5 of 12). The difference in the P-gp expression in the two groups was statistically significant (P = 0.0042). Among the well differentiated (WD) tumors (4 of 49), 50% (2 of 4) had high expression and among the well differentiated (PD) tumors (45 of 49), 11.1% (5 of 45) had a high P-gp expression. There was no statistically significant difference with P-gp expression in relation to tumor differentiation, laterality, and presence of high-risk histopathological features.

From India, there has been one other study in which Krishnakumar et al. analyzed P-gp expression by imunohistochemistry prior to chemotherapy and studied the long-term follow-up. [4] In our study we found that 58.3% (7 of 12) retinoblastoma cases enucleated after chemotherapy had high expression of P-gp as compared with 27.0% (10 of 37) primarily enucleated cases. This significant difference in P-gp expression indicates that chemotherapy might have selected resistant clones of cells expressing high P-gp.

Though there have been a few studies studying the expression of P-gp in retinoblastoma and its relation to drug resistance, these were retrospective studies and the practical implication have not yet been well considered. [4],[5],[6] However, the high P-gp expression in chemotreated eyes in our study and in few other studies support that chemotherapy may have some role in high expression of P-gp in retinoblastoma. These findings could have important implications in understanding the mechanism of chemoresistance in retinoblastoma patients, and warrant further prospective investigation in a larger patient population.

 
   References Top

1.Kivelä T. The epidemiological challenge of the most frequent eye cancer: Retinoblastoma, an issue of birth and death. Br J Ophthalmol 2009;93:1129-31.  Back to cited text no. 1
    
2.Chan HS, Thorner PS, Haddad G, Ling V. Immunohistochemical detection of P-glycoprotein: Prognostic correlation in soft tissue sarcoma of childhood. J Clin Oncol 1990;8:689-704.  Back to cited text no. 2
    
3.Chan HS, Thorner PS, Haddad G, Gallie BL. Multidrug-resistant phenotype in retinoblastoma correlates with P-glycoprotein expression. Ophthalmology 1991;98:1425-31.  Back to cited text no. 3
    
4.Krishnakumar S, Mallikarjuna K, Desai N, Muthialu A, Venkatesan N, Sundaram A, et al. Multidrug resistant proteins: P-glycoprotein and lung resistance protein expression in retinoblastoma. Br J Ophthalmol 2004;88:1521-6.  Back to cited text no. 4
    
5.Filho JP, Correa ZM, Odashiro AN, Coutinho AB, Martins MC, Erwenne CM, et al. Histopathological features and P-glycoprotein expression in retinoblastoma. Invest Ophthalmol Vis Sci 2005;46:3478-83.  Back to cited text no. 5
    
6.Souza Filho JP, Martins MC, Caissie AL, Torres VL, Fernandes LH, Erwenne CM, et al. Relationship between histopathological features of chemotherapy treated retinoblastoma and P-glycoprotein expression. Clin Experiment Ophthalmol 2005;33:279-84.  Back to cited text no. 6
    


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