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Nur Khatib, Jacob Pe'er, Radgonde Amer; Tumor-infiltrating Foxp3+ Regulatory T Cells In Posterior Uveal Melanoma: Clinicopathologic Correlation. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1452.
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Regulatory T cells (Tregs) have potent immunosuppressive abilities contributing to tumor evasion from the immune system. Increased numbers of Tregs were detected in malignant lesions, sentinel lymph nodes, and peripheral blood from cancer patients in a variety of malignant diseases and were associated with poor survival in various malignancies. The aim of this study was to examine the expression of Foxp3 in uveal melanoma and to correlate it with clinicopathologic parameters.
Foxp3 expression was immunohistochemically evaluated in primary tumors of 77 patients who underwent enucleation at Hadassah-Hebrew University Hospital between the years (1986-2006). Nineteen metastatic liver sections were also stained.
Forty-five tumors were from females; age range was between 19 and 86 years (mean 60.7 y). Fifty-nine tumors were Foxp3 positive whereas 18 were Foxp3 negative. Of the epithelioid/mixed-type tumors (n=59), 45 were Foxp3 positive (76.3%) whereas of the spindle-type tumors (n=16), 13 were Foxp3 positive (81.3%). Of the tumors located in the choroid (n=41), 30 were Foxp3 positive (73%), whereas of the tumors located in the ciliary body (n=35), 29 were Foxp3 positive (82.9%). With regard to the extracellular matrix pattern; of the silent/normal pattern (n=24), 12 were Foxp3 positive (50%) whereas of the network/loops/parallel with cross-link patterns (n= 30), 27 were Foxp3 positive (90%) (p=0.001); there was an increased odds of developing a higher vascular pattern in Foxp3-positive tumors (OR=9.0, 95% CI=2.14-38.46). Mean tumor diameter was 13.68 mm ±SD 3.45 for Foxp3-negative tumors, whereas it was 14.56 mm ± SD 4.25 for Foxp3-positive tumors. Mean tumor height was 9.71 mm ± SD 3.42 for Foxp3-negative tumors and 10.36 mm ± SD 3.68 for Foxp3-positive tumors. In patients who developed liver metastasis (n=32), 27 were Foxp3 positive (84.4%) whereas in patients without metastasis (n=24), 16 were Foxp3 positive (66.7%) (p=0.12). No information was available on the remaining 21 patients. Nineteen liver metastatic sections were also studied; 16 were found to positively express Foxp3.
We were able to detect Foxp3-positive Tregs in approximately 77% of posterior uveal melanoma samples. No correlation was demonstrated between the expression of Foxp3 and tumor size, location, cell type and metastasis. However, a significant correlation was shown with the higher vascular patterns. To develop novel therapeutic strategies, we must gain insight into the mechanisms of Treg control and regulation in uveal melanomas.
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