Role of HMG protein in Primary Retinoblastoma

Abstract

Purpose: Retinoblastoma is a malignant tumor composed of embryonic tumor cells from retinoblasts of neuroepithelial origin. High mobility group proteins (HMG) are the member of non histone nuclear factors associated with cell proliferation, differentiation and neoplastic transformation. High mobility group (HMG) proteins is a newly recognized protein regulating cancer cell tumorigenesis, expansion and invasion. However, the role of HMGB1 is still unclear in retinoblastoma.

Methods: Prospective analysis of 70 primary enucleated retinoblastoma cases over a period of one year. Expression of HMGB1 was performed by immunohistochemistry (IHC) in formalin fixed retinoblastoma specimens and their results were confirmed by western blotting. mRNA expression was performed by semi-quantitative Reverse Transcriptase PCR (RT-PCR).

Results: A total of 70 eyes were taken of which 10(14.28%) eyes had bilateral involvement. Ages ranged from 7months to 8years. 56 (80%) cases were reported as poorly differentiated tumors whereas 46(65.71%) and 14(20%) cases had calcification and necrosis respectively. Histopathologically, 16(22.85%) had massive choroid invasion, 13(18.57%) had optic nerve invasion, 6 cases each had scleral and ciliary body invasion. Strong expression of HMGB1 were seen in 41/70(58.57%) cases. mRNA expression was seen in 36 cases (51.4%) by RT-PCR. Expression of HMGB1 was statistically significant with poor differentiation (p=0.0436) and optic nerve invasion (p=0.0473).

Conclusions: Overexpression of HMGB1 is seen more in poorly differentiated tumors and those with, histopathological high risk factors. HMGB1 could serve as a poor prognostic marker in retinoblastoma. Better understanding of the molecular mechanisms underlying HMGB1 function could yield novel therapeutic approaches to anti-cancer strategies.

Keywords: 703 retinoblastoma • 624 oncology • 554 immunohistochemistry