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A. Solomon, R. Yutav, J. Frucht–Pery, J. Pe'er; Increased Tissue Expression of IGFBP–2 in Ocular Surface Pigmented Neoplasia . Invest. Ophthalmol. Vis. Sci. 2005;46(13):3366.
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Purpose: Increased IGFBP–2 tissue expression and its high serum levels have been noted in various malignancies, including prostate carcinoma, malignant ovarian tumors, colon tumors and others. The purpose of this study was to investigate the tissue expression of IGFBP–2 in various pigmented tumors of the ocular surface. Methods: Tissue sections were prepared from paraffin–embedded formalin– fixed blocks of conjunctival samples removed from 21 patients with primary acquired melanosis (PAM), ten patients with conjunctival nevus, and 17 patients with conjunctival melanoma. Tissue sections from 10 age–matched eyes enucleated because of trauma served as controls. Expression of IGFBP2 in the conjunctival epithelium was evaluated by immunohistochemistry using rabbit anti–human polyclonal antibodies for these proteins. Digital image analysis was performed to quantify the tissue expression of IGFBP–2. A mean intensity stain index (ISI), based on the staining density and the area stained, was calculated from digital images captured from sequential areas of microscopic sections in each coverslip. The mean ISI of sections from patients with PAM, conjunctival nevi and melanomas was compared to that of controls. Results: The expression of IGFBP–2 was signficantly higher in all the pigmented tumors compared to controls. The mean ISI values were 141.21 ± 116.64 in PAM; 42.73 ± 18.29 in conjunctival nevus; 49.33 ± 27.49 in conjunctival melanoma; and 0.52 ± 0.53 in control samples (p<0.0001, one way ANOVA). A signficant difference was demonstrated between the expression of IGFBP–2 in PAM with atypia (234.77 ± 118.84) and PAM without atypia (62.03 ± 30.98, p=0.017). The expression of IGFBP–2 was evident mainly in the cytoplasm of melanocytes and conjunctival epithelial cells, as well as throughout the extracellular matrix. In conjunctival melanoma, IGFBP–2 was also evident in macrophages. Conclusions: IGFBP–2 is highly expressed in pigmented tumors of the ocular surface, and may serve as a positive marker for these lesions. Identification of IGFBP–2 in the tears or in the serum may be used to evalute the proliferative nature of the lesion, and to detect recurrence following excision.
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