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Matthew Balazsi, Patricia R. Odashiro, Sebastian Di Cesare, Mohib Morcos, Patrick Logan, Miguel N. Burnier, Jr.; Expression of Secreted Frizzled-Related Protein 1 (SFRP-1) in Retinoblastoma. Invest. Ophthalmol. Vis. Sci. 2011;52(14):2475.
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The Wingless and Int1 (Wnt) signaling pathway is responsible for the regulation of various cellular developmental processes including cell proliferation, differentiation and apoptosis. Among the extracellular Wnt inhibitors, the secreted frizzled-related proteins (SFRPs) are decoy receptors and one of the largest families of Wnt antagonists. Loss of SFRP-1 and stimulation of the Wnt pathway have been reported in tumors of various organs, including colon, lung, breast, ovary, and stomach. The aim of this study is to investigate the immunohistochemical expression of SFRP-1 in RB.
Formalin-fixed, paraffin-embedded tissue from 20 cases of RB was analyzed. Immunohistochemistry for SFRP-1 (ab4193) was performed using a fully automated Ventan Benchmark system. Levels of expression were classified according to the intensity (0: negative; 1: weak; 2: moderate, 3: strong) and percentage of positive tumor cells (0: negative; 1: 1-10%; 2: 11-50%; 3: 51-80%; 4: 81-100%). The data was then converted to the German ImmunoReactive Score (IRS) by multiplying the quantity and staining intensity scores. The final immunohistochemical score was correlated to histopathological prognostic features such as vitreous seeding, extension of necrosis, choroidal, anterior chamber, and optic nerve invasion using the students T-test.
Sixteen cases (80%) of RB cases were positive for SFRP-1, but none with strong expression. According to the IRS, the positive cases were classified as follows: 3 cases (15%) scored 1; 3 cases (15%) scored 2; 1 case (5%) scored 3; 7 cases (35%) scored 4; 1 case (5%) scored 6; 1 case (5%) scored 8. Four cases were classified as negative (score 0). There was a significant correlation between IRS and vitreous seeding (p=0.032). Although statistical significance not reached, the extent of necrosis and IRS score showed a trend (p=0.069). There was no correlation of IRS with other histopathological features.
To the best of our knowledge, this is the first time that the expression of SFRP-1 has been investigated in a RB series. SFRP-1 is expressed in low levels in the majority of RB cases. There was a positive correlation between tumors with high IRS score and markers of rapidly growing RB. These findings are contradictory to other tumors in which SFRP-1 is expressed. Although the exact reason for this contradiction is unknown, it may be due to the neurogenic nature of RB. More studies investigating the role of SFRP-1 in RB are warranted.
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