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Lynn Schoenfield, Paula Carver, Ray Tubbs, Charles Biscotti, Arun D. Singh; Immunoperoxidase Staining For c-MET In Uveal Melanoma And Metastases. Invest. Ophthalmol. Vis. Sci. 2011;52(14):1444.
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This study was undertaken to get further experience with immunoperoxidase staining of c-MET in uveal melanomas as well as in liver metastases. MET is a proto-oncogene which has been found to be deregulated in several malignancies, including carcinomas, sarcomas, hematologic malignancies, and glioblastoma. The most common genetic alteration is gene amplification leading to over-expression of MET. Evaluation of tumor expression may prove helpful as treatments aimed at modulating this gene are currently under investigation.
21 enucleated eyes for uveal melanoma were immunostained for c-MET. Liver (3 cases) and bone metastases (1 case) were also examined. Immunohistochemistry on FFPE tissue was performed with antigen retrieval on a Discovery XT automated stainer (Ventana, Tuscon, AZ). The primary c-MET (ab51067) antibody (rabbit monoclonal, Abcam, Cambridge, MA) was followed by a secondary antibody (UltraMap anti-Rb AP; Ventana) and ChromoMap Red (Ventana) was used for detection. Cells were then counterstained with hematoxylin and visualized by light microscopy. Staining was scored as follows: 0, no staining, 1, <10% cells, 2, 10-50% cells, and 3, >50% cells staining. The results were correlated with FISH results for monosomy 3 and clinical follow-up where available.
The enucleations were from 11 men and 10 women aged 40-86 (mean 65 yrs). FISH for monosomy 3 was done in 16 patients, and follow-up ranged from 1 month to 5 years. There were10 choroidal and 11 cilichoroidal melanomas. At the end of this study 6 patients had died (5 with known hepatic metastases, monosomy 3 and positive immunostaining for c-MET (1+ to 3+). The fifth case was monosomy 3 but negative for c-MET. Two cases were negative for c-MET, 1 with disomy 3 and the other with no FISH available; both patients are alive at 3 yrs. and 3 mo. respectively. The remaining 13 cases showed positive staining ranging from 1+ to 3+, which was often focal, the significance of which is unclear. One patient with 3+ staining is known to have liver metastasis; follow-up ranges from 1 mo to 4 years in this group. The 3 liver metastases studied showed positive staining, as did the bone (vertebral body) metastasis.
While positive staining was found in 5 of 6 cases of death due to liver metastasis and 1 case of bone metastases, the findings are at this time inconclusive, due to insufficient time for follow-up. Further study is warranted, including evaluating the possible stratification of patients based on intensity of positive staining and locality within the tumor, which might reveal differences in tumor clones.
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