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P. Zimmermann, T. Dietrich, F. Bock, C. Rummelt, F. E. Kruse, C. Cursiefen; Tumor-Associated Lymphangiogenesis as Novel Prognostic Marker for Metastasis of Conjunctival Malignant Melanomas. Invest. Ophthalmol. Vis. Sci. 2007;48(13):4799.
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Conjunctival malignant melanomas (cMM) often lead to recurrence and lymphatic metastasis. Tumor-associated lymphangiogenesis has recently been shown to be a novel prognostic marker for metastasis of skin melanomas. Purpose of the study was to evaluate, whether tumor-associated lymphangiogenesis might be a novel prognostic marker for the risk of metastasis of cMM, too.
Clinical files and conjunctival specimen of 20 patients with histologically proven cMM were analysed. First, sections of conjunctival specimen, embedded in paraffin, were stained with LYVE-1, as a novel specific marker for lymphatic endothelium. Thereafter, digital photos of the tumor and adjacent tissue were analysed by Image J software. The tumor area, area covered by lymphatic vessels (LVA) and number of vessels (LVN) in the tumor itself and in the adjacent tissue (50 µm and 200 µm from the tumor edge) were measured. These results were related to clinical data e.g. about metastasis.
By LYVE-1 staining, lymphatic vessels were identified in all specimens, both within the tumor and in the adjacent tissue. Mitomycin-C treated tumors had a significantly reduced LVA both intratumorally (p<0.03) and 50 µm-peritumorally (p<0.05) compared to patients without Mitomycin-treatment. The extent of tumor lymphangiogenesis was significantly related to rate of metastasis. Significantly larger tumor size (p<0.04) and higher LVA (p<0.04) and LVN (p<0.04) in the tissue 50 µm around the tumor margins were found in patient with metastasis compared to patients with no metastasis. The different cMM subtypes have a different lymphangiogenic potential: spindle-cell cMM showed more LVN intratumorally and in the adjacent tissue compared to mixed-cell cMM and epithelioid-cell cMM.
Lymphatic vessels were detected in all cMM analyzed, both within the tumor itself and in the tumor adjacent tissue. Intra- and peritumoral lymphangiogenesis were related to the risk of metastasis. Therefore, lymphangiogenesis seems to play an important role in the metastatic spread of cMM. This may open new treatment avenues for anti-lymphangiogenic therapies to prevent lymphatic tumor metastasis.
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