Pereira Patricia Rusa, Odashiro Alexandre Nakao, Marshall Jean Claude, Correa Zelia Maria, Belfort Rubens, Burnier Miguel N
Department of Ophthalmology, Federal University of São Paulo, São Paulo, Brazil.
J Carcinog. 2005 Oct 19;4:19. doi: 10.1186/1477-3163-4-19.
Uveal melanoma (UM) is the most common primary intraocular tumor in adults, leading to metastasis in 40% of the cases and ultimately to death in 10 years, despite local and/or systemic treatment. The c-kit protein (CD117) is a membrane-bound tyrosine kinase receptor and its overexpression has been observed in several neoplasms. Imatinib mesylate is a FDA approved compound that inhibits tyrosine quinase receptors, as well as c-kit. Imatinib mesylate controls tumor growth in up to 85% of advanced gastrointestinal stromal tumors, a neoplasia resistant to conventional therapy.
Fifty-five specimens of primary UM selected from the archives of the Ocular Pathology Laboratory, McGill University, Montreal, Canada, were immunostained for c-kit. All cells displaying distinct immunoreactivity were considered positive. Four human UM cell lines and 1 human uveal transformed melanocyte cell line were tested for in vitro proliferation Assays (TOX-6) and invasion assay with imatinib mesylate (concentration of 10 microM).
The c-kit expression was positive in 78.2% of the UM. There was a statistical significant decrease in the proliferation and invasion rates of all 5 cell lines.
The majority of UM expressed c-kit, and imatinib mesylate does decrease the proliferation and invasion rates of human UM cell lines. These results justify the need for a clinical trial to investigate in vivo the response of UM to imatinib mesylate.
葡萄膜黑色素瘤（UM）是成人中最常见的原发性眼内肿瘤，尽管进行了局部和/或全身治疗，但仍有40%的病例会发生转移，最终在10年内导致死亡。c-kit蛋白（CD117）是一种膜结合酪氨酸激酶受体，在几种肿瘤中均观察到其过表达。甲磺酸伊马替尼是一种经美国食品药品监督管理局（FDA）批准的化合物，可抑制酪氨酸激酶受体以及c-kit。甲磺酸伊马替尼可控制高达85%的晚期胃肠道间质瘤（一种对传统治疗耐药的肿瘤）的肿瘤生长。
从加拿大蒙特利尔麦吉尔大学眼病理实验室存档中选取55例原发性UM标本，进行c-kit免疫染色。所有显示明显免疫反应性的细胞均被视为阳性。对4种人UM细胞系和1种人葡萄膜转化黑素细胞系进行体外增殖试验（TOX-6）和甲磺酸伊马替尼（浓度为10微摩尔）侵袭试验。
78.2%的UM中c-kit表达呈阳性。所有5种细胞系的增殖和侵袭率均有统计学意义的下降。
大多数UM表达c-kit，甲磺酸伊马替尼确实可降低人UM细胞系的增殖和侵袭率。这些结果证明有必要进行一项临床试验，以研究UM在体内对甲磺酸伊马替尼的反应。
