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Seema Kashyap, Lata Singh, Neelam Pushker, Seema Sen, Anjana Sharma, Bhavna Chawla, NO; Histopathological Analysis of Cell Division Cycle 25 (CDC25) Phosphatase Protein in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2014;55(13):3080.
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Retinoblastoma is the most common childhood intraocular malignant tumor of the developing retina . Cell Division Cycle 25 (CDC25) phosphatase is an essential regulator of the cell cycle machinery, functioning as a positive regulator by activating Cyclin-Dependent Kinases (CDK). CDC25A plays a pivotal role in controlling cell proliferation during development and tumorigenesis. Overexpression of CDC25A is detected in a number of tumors which implies dysregulation in malignant transformation. However, the role of CDC25A in patients with Retinoblastoma is still unknown.
Prospective analyses of 60 primary enucleated retinoblastoma cases over a period of one year (Jan 2011-Dec 2012). CDC25A protein expression was investigated by Immunohistochemistry in formalin fixed paraffin embedded sections and then validated by western blotting. Cytoplasmic staining was graded as weak/negative (1+), moderate (2+) and strong (3+). Semi-quantitative analysis for expression of CDC25A mRNA was performed by the Reverse-Transcriptase PCR (RT-PCR). Expression of CDC25A was correlated with tumor differentiation and various histopathological high risk factors.
There were total of 45 poorly differentiated retinoblastomas and 15 well differentiated retinoblastomas. Necrosis and calcification was found in 37 (61.6%) and 17 (28.3%) respectively. Massive choroidal invasion, optic nerve invasion and scleral invasion was found in 20/60, 17/60 and 7/60 cases respectively. Immunohistochemistry showed CDC25A expression in total of 38/60 (63.3%) cases. Western blotting was performed to confirm immunoreactivity results on representative cases. mRNA expression was seen in 31/60 (51.6%) cases by RT-PCR. Expression of CDC25A showed statistically significant correlation with poor tumour differentiation and tumor invasion (p<0.05).
Our results suggest that increased expression of CDC25A plays an important role in the pathogenesis of retinoblastoma. CDC25A was associated with invasion of ocular coats and poor differentiation. CDC25A expression might be a potential molecular target for novel drug development in tumor biology.
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