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E.L. Chang, C.R. Bernardino, P.A. Rubin, B.R. Ksander; Primary Tumor Growth and Metastatic Spread of Human Conjunctival Melanomas in an Animal Model . Invest. Ophthalmol. Vis. Sci. 2003;44(13):2429.
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© ARVO (1962-2015); The Authors (2016-present)
Purpose: Malignant melanoma of the conjunctiva is a malignancy characterized by a high recurrence rate (51.8%) and a 10-year-mortality rate of 26%. There are no animal models to test novel therapeutic treatments that could prevent metastatic spread. An ideal animal model would: (i) utilize human conjunctival melanoma tissue, (ii) grow orthotopically within the conjunctiva (iii) follow a natural progression from primary to metastatic disease, and (iv) metastasize to sites typically found in the human disease. Methods: A recurrent melanoma was excised from the conjunctiva of a 69-year-old patient. No systemic disease was detected at the time of tumor excision and the patient currently remains free of metastases. A representative tumor section was analyzed by pathology; the remainder of the tumor was used in this study. Using sterile technique and working under a sterile laminar flow hood, tumor fragments were placed in petri dishes and necrotic tumor tissue was excised. Specimens were cut into pieces 1mm3 in size and tumor fragments were surgically grafted into the conjunctiva of SCID (severe combined immunodeficient) mice, which were used to prevent rejection of the xenogeneic human tumor specimens. Mice were sacrificed 4 months after implantation. All internal organs were inspected macroscopically at the time of autopsy with special attention given to the regional lymph nodes, liver and spleen. Results: Orthotopically implanted conjunctival melanomas were observed at regular intervals throughout the study. Early after implantation the tumors became vascularized. After three months there was only slight increases in tumor size in 2/3 of the mice. In the 4th month, two mice developed metastases in the ipsilateral submandibular lymph node. Histopathological analysis of these mice revealed local proliferation of tumor cells within the conjunctiva with metastasis to the ipsilateral submandibular gland, liver and spleen. Tissue sections were stained with H&E, HMB45 and S100 to confirm the presence of human conjunctiva melanoma cells at each of the metastatic locations. Conclusions: Orthotopic xenografts of human conjunctival melanoma into immunocompromised mice produced a model in which primary tumor growth and metastatic spread followed the human disease. This model will not only provide an opportunity to test the effectiveness of anti-tumor and anti-metastatic therapies, but will also provide the opportunity to analyze the changes in tumor cell biology that coincide with disease progression.
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