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Hans E Grossniklaus, Qing Zhang, Hua Yang, Shou You, Shin Kang; Progression of Ocular Melanoma Metastasis to the Liver in Mouse Model. Invest. Ophthalmol. Vis. Sci. 2014;55(13):5073.
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To test the hypothesis that the histological and immunohistochemical findings in metastatic human uveal melanoma to the liver in a mouse model are similar to metastatic uveal melanoma to the liver in humans.
Human uveal melanoma cell line Mel290 were cultured, and inoculated into the superchoroidal space in the right eyes of NU:NU mice via trans-scleral technique. The tumor-burden eyes were enucleated at the 7th day to determine primary tumor growth, and the livers were collected at the 1, 2, 6, or 12 weeks to determine the hepatic metastases. Histological examination and immunohistochemical staining were then performed.
Stage 1 metastases (defined as tumor clusters less than 50 μm in diameter) were identified in the sinusoidal spaces of 10 of 12 mice (83%). Stage 1 metastases were avascular and lacked mitotic activity. Stage 2 metastases (defined as tumors measuring 51-200 μm in diameter) were found in 8 mice sacrificed at the 6 or 12 weeks. Stage 3 metastases (defined as tumors measuring greater than 200 μm in diameter) were found in 4 mice sacrificed at 12 weeks. Immunohistochemical stains were positive for S100 or HMB45 in all tumors. Overall, stage 1 metastases out-numbered stage 2 metastases , which out-numbered stage 3 metastases (P less than 0.0001 and P less than 0.005, respectively). The mean vascular density and mitotic index increased from stage 1 to stage 3 metastases (P less than 0.01). The architecture of stage 2 metastases mimicked the surrounding hepatic parenchyma, with pseudosinusoidal spaces metastases stained with reticulin and lined by smooth muscle actin-positive activated stellate cells (myofibroblasts), whereas stage 3 metastases exhibited either lobular or portal growth patterns with tumor vascularization.
The in vivo mouse model of human uveal melanoma is reliable and reproducible, and forms hepatic metastases which can be categorized as stage 1 micro-, stage 2 intermediate-, or stage 3 vascularized and mitotically active macro-metastases with a lobular or portal pattern of growth that mimics metastatic uveal melanoma to the liver in humans.
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