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S. A. Callejo, E. Antecka, J. Marshall, M. Burnier, Jr.; Early Subclinical Extraocular Disease in Uveal Melanoma. An Animal Model. Invest. Ophthalmol. Vis. Sci. 2008;49(13):29. doi: https://doi.org/.
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© ARVO (1962-2015); The Authors (2016-present)
Metastasis is the major cause of treatment failure and death in uveal melanoma patients (UMP). The majority of UMP do not show clinical, radiological or biochemical evidence of metastases upon diagnosis. Despite excellent local tumor control, 40% of UMP will progress to develop metastases 6 to 10 years later. These findings suggest that tumor cells (TC) have already disseminated by the time of initial diagnosis and UMP may have undetectable subclinical systemic disease. The purpose of the study was to elucidate early steps of subclinical micrometastatic formation.
Human UM cells were injected into the suprachoroidal space of 10 immunosuppressed rabbits. One rabbit per week was sacrificed and the liver, the lungs, and the kidneys were collected. In order to assess for the presence of TC within the extravascular space, the blood contained within one kidney, one lung and a lobe of liver from each rabbit was flushed out of the organs using sterile saline injected through the main arteries. The tissue was then homogenized and processed using Real-Time-PCR to detect the presence of disseminated TC. In order to assess for the presence of TC within the intravascular and extravascular space, second lung, kidney and lobe of liver were individually processed as a homogenization of both tissue and blood, and processed using Real-Time-PCR.
All organs tested negative during the first week following intraocular implantation. In the second week, TC were found in the non-flushed liver only. During the third week, only the non-flushed lung tested positive. At week 4, non-flushed liver and lung and flushed lung were positive. From week 5 until the end of the experiment all flushed and non-flushed livers and lungs were positive. The kidneys, flushed and non-flushed, remained negative through out the experiment.
This study confirms the presence of early subclinical extraocular disease in UM. It also provides with unobserved clues of TC dissemination and extravascular TC implantation. In the early stages of dissemination, TC are found within the intravascular space. As the disease progresses, TC are also present in the extravascular space, as suggested by the presence of positive results in flushed organs. Local host tissue-TC interaction may account for the arrest and persistence of TC in permissive organs such as lung and liver, while a negative interaction takes place in other organs such as kidney. Better understanding of the interactions between TC and permissive and non-permissive organs may facilitate the development of new adjuvant therapies.
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