Missotten Guy S, Journée-de Korver Johanna G, de Wolff-Rouendaal Didi, Keunen Jan E, Schlingemann Reinier O, Jager Martine J
Department of Ophthalmology, Leiden University Medical Center, University of Leiden, Leiden, The Netherlands.
Invest Ophthalmol Vis Sci. 2003 Jul;44(7):3059-65. doi: 10.1167/iovs.02-1038.
Expression of heat shock proteins (HSPs) is of prognostic significance in several tumor types, whereas HSPs may also have clinical use as stimulators in tumor vaccination. HSP expression levels were determined in normal eyes and in uveal melanoma and tested whether HSPs expression was associated with prognostic parameters in the uveal melanoma.
Expression of HSP27, HSP70, HSP90, and glycoprotein96 (GP96) were determined on paraffin-embedded and frozen sections from seven healthy eyes, 20 primary uveal melanomas without prior treatment, and 18 uveal melanomas after prior treatment. HSP expression was determined by alkaline phosphatase-anti-alkaline phosphatase (APAAP) immunohistochemistry, using appropriate monoclonal antibodies and scored semiquantitatively. Expression of HSPs was validated on retinal tissue of a normal eye and in two uveal melanoma cell lines by Western blot analysis.
Expression of HSPs was observed in epithelial and pigment cells of the normal eyes. In uveal melanoma, the level of expression of HSPs varied. Expression of HSP27 and GP96 was noted in more than 30 of 38 uveal melanomas (with, respectively, a mean of 66% and 53% positive cells). HSP70 and HSP90 were expressed in 6% of tumor cells. The amount of expression of any of the HSP types was not significantly associated with known prognostic factors. There was not a significant difference in expression of the HSPs between uveal melanomas with or without any type of prior treatment.
In this study, expression of HSPs in uveal melanoma is not correlated with known histopathologic prognostic factors. The high expression of GP96 indicates that this protein is a potential vector in tumor vaccination in patients with large uveal melanomas.
热休克蛋白（HSPs）的表达在多种肿瘤类型中具有预后意义，而HSPs也可作为肿瘤疫苗接种中的刺激物用于临床。本研究测定了正常眼和葡萄膜黑色素瘤中HSPs的表达水平，并检测HSPs表达是否与葡萄膜黑色素瘤的预后参数相关。
采用碱性磷酸酶抗碱性磷酸酶（APAAP）免疫组织化学方法，使用适当的单克隆抗体，对7只健康眼、20例未经治疗的原发性葡萄膜黑色素瘤以及18例经治疗后的葡萄膜黑色素瘤的石蜡包埋切片和冰冻切片进行HSP27、HSP70、HSP90和糖蛋白96（GP96）表达的测定，并进行半定量评分。通过蛋白质免疫印迹分析在正常眼视网膜组织和两种葡萄膜黑色素瘤细胞系中验证HSPs的表达。
在正常眼的上皮细胞和色素细胞中观察到HSPs的表达。在葡萄膜黑色素瘤中，HSPs的表达水平各不相同。在38例葡萄膜黑色素瘤中的30多例中检测到HSP27和GP96的表达（阳性细胞平均分别为66%和53%）。HSP70和HSP90在6%的肿瘤细胞中表达。任何一种HSP类型的表达量与已知的预后因素均无显著相关性。有无任何类型前期治疗的葡萄膜黑色素瘤之间HSPs的表达无显著差异。
在本研究中，葡萄膜黑色素瘤中HSPs的表达与已知的组织病理学预后因素无关。GP96的高表达表明该蛋白是葡萄膜黑色素瘤患者肿瘤疫苗接种中的潜在载体。
