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nadine marques, Ana Beatriz Toledo Dias, Sarah Alghamdi, Cristina Fonseca, Tânia Borges, Miguel N Burnier; PAR-1 and Maspin expression in Retinoblastoma and their correlation with histopathological prognostic features . Invest. Ophthalmol. Vis. Sci. 2015;56(7 ):79.
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Maspin is a tumor suppressor protein expressed in normal mammary and other epithelial cells and is reduced or absent in breast, ovarian carcinomas, and gliomas. Protease activated receptor 1 (PAR-1) is related to tumor growth and metastatic potential. Maspin expression, when co-expressed with PAR-1, can counteract its malignant potential, as the maspin gene is downstream of PAR-1 signaling. Our purpose was to evaluate, for the first time, maspin and PAR-1 expression in retinoblastomas and in normal retinas, and to correlate them with histopathological prognostic features.
Maspin and PAR-1 expression were evaluated in 40 retinoblastoma eyes. Nine normal human eyes from the Eye Bank of Canada were used as controls. Positive controls were skin for maspin and pancreas for PAR-1. Maspin and PAR-1 immunostains were evaluated using a score considering extent of tumor/structure staining (0=none, 1=<50% and 2=>50%) and intensity (0=none, 1=intensity < positive controls, 2=intensity > positive controls). A total final score ranging between 0 and 4 was established (final score = proportion x intensity of staining). Invasive phenotype was considered when invasion of the optic nerve or choroid were present. Fisher exact and Student’s t-test analyses was performed to compare variables.
A maspin score of 0 (neither nuclear nor cytoplasmic expression) correlated with invasive phenotype (P=0.03). No difference in invasive phenotype was found for isolated PAR-1 or PAR-1 without maspin expression in the same tumor. In normal eyes, no nuclear or cytoplasmic maspin staining in the retina was found. Both retinal plexiform layers showed PAR-1 expression in 6 of the same samples (4 with score 2 and 2 with score 4). No differences in PAR-1 score between normal retinas and retinoblastoma were found.
Absence of maspin expression is associated with more aggressive biological behavior in this study. PAR-1 expression was found only in plexiform layers of normal retinas and does not differ according to retinoblastoma expression score. Maspin is not expressed in the normal retina. The identification of maspin suggests that it may be a novel therapeutic target for aggressive retinoblastomas.
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