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D.-M. Sanft, R. Kwee, P. Logan, C. Martins, E. Antecka, M. N. Burnier, Jr.; The Correlation Between KAI1 Expression and Uveal Melanoma Prognosis. Invest. Ophthalmol. Vis. Sci. 2009;50(13):5769.
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Uveal melanoma (UM) is the most common malignant primary intraocular tumor in adults. Approximately 50% of UM patients develop metastasis within ten years of initial diagnosis. KAI1, a human metastasis suppressor gene, is thought to work in the dormancy phase of metastasis. The purpose of this study was to investigate the expression of KAI1 in uveal melanoma and determine its potential as a prognostic factor.
Sixteen formalin-fixed, paraffin-embedded human UM specimens were immunostained with a mouse anti-human KAI1 antibody and were compared with clinical pathological data, including survival time. The positive control for the KAI1 antibody was human breast carcinoma tissue. Inclusion criteria included a minimum follow-up of 60 months for patients with no metastasis. Each specimen was graded based on the intensity and extent of the immunostaining. Intensity was categorized as negative, mild or strong. The extent was classified as negative, focal or diffuse. If less than 30% of the tumor was stained, the specimen was classified as focal. Conversely, if more than 30% of the tumor was stained, it was classified as diffuse. A Fisher Exact Test was used to determine if the absence of KAI1 expression correlated with metastatic disease.
The immunohistochemical results of KAI1 expression displayed cytoplasmic staining in 11 of 16 (69%) UM specimens. Two specimens were graded as focal, nine specimens as diffuse, and five specimens did not stain. Three of the 11 (27%) cases staining positive for KAI1 were derived from patients with metastasis. All (100%) of the 5 KAI1-negative cases were derived from patients with metastasis. This correlation between KAI1 staining and metastasis was statistically significant (Fisher Exact test, p=0.02).
To the best of our knowledge, this is the first time that KAI1 expression has been investigated in UM. The absence of KAI1 expression is significantly correlated with metastatic disease, suggesting that KAI1 may represent a potential prognostic factor in UM. Furthermore, upregulation of KAI1 may be effective in preventing metastatic development in this particular tumor.
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