Maat Willem, Ly Long V, Jordanova Ekaterina S, de Wolff-Rouendaal Didi, Schalij-Delfos Nicoline E, Jager Martine J
Department of Ophthalmology, Leiden University Medical Center, Leiden, The Netherlands.
Invest Ophthalmol Vis Sci. 2008 Feb;49(2):505-10. doi: 10.1167/iovs.07-0786.
In uveal melanoma, different predictors of poor prognosis have been identified, including monosomy of chromosome 3, HLA expression, and the presence of infiltrating leukocytes and macrophages. Each of these parameters can be used to differentiate prognostically the favorable tumors from the unfavorable ones, and thus the hypothesis for the present study was that they are related, and that monosomy of chromosome 3 occurs in the same tumors as the unfavorable inflammatory phenotype.
Tumor tissue was obtained from 50 cases of uveal melanoma treated between 1999 and 2004. After enucleation, nuclei were isolated from paraffin-embedded tissue for fluorescence in situ hybridization, to determine the chromosome 3 copy number. Each tumor-containing globe was further processed for conventional histopathologic examination and for immunohistochemical analysis with HLA class I and II-specific antibodies and with macrophage marker CD68.
Of 50 uveal melanomas, 62% (31/50) were categorized as having monosomy of chromosome 3. Monosomy 3 was associated with the presence of epithelioid cells, an increased density of tumor-infiltrating macrophages, and a higher HLA class I and II expression. Survival analyses showed a correlation between monosomy 3 and decreased survival and identified monosomy 3, ciliary body involvement, and largest basal tumor diameter as the best prognostic markers.
Monosomy 3 in uveal melanoma is associated with the presence of an inflammatory phenotype, consisting of a high HLA class I and II expression as well as an increased number of tumor-infiltrating macrophages. In a multivariate Cox regression analysis, the presence of monosomy 3 was one of the best prognostic markers of metastatic disease and survival, although the follow-up time was short.
在葡萄膜黑色素瘤中，已确定了不同的预后不良预测指标，包括3号染色体单体性、HLA表达以及浸润性白细胞和巨噬细胞的存在。这些参数中的每一个都可用于在预后方面区分预后良好的肿瘤和预后不良的肿瘤，因此本研究的假设是它们之间存在关联，并且3号染色体单体性出现在与不良炎症表型相同的肿瘤中。
从1999年至2004年接受治疗的50例葡萄膜黑色素瘤患者中获取肿瘤组织。眼球摘除后，从石蜡包埋组织中分离细胞核用于荧光原位杂交，以确定3号染色体的拷贝数。对每个含有肿瘤的眼球进一步进行常规组织病理学检查以及使用HLA I类和II类特异性抗体和巨噬细胞标志物CD68进行免疫组织化学分析。
在50例葡萄膜黑色素瘤中，62%（31/50）被归类为具有3号染色体单体性。3号染色体单体性与上皮样细胞的存在、肿瘤浸润巨噬细胞密度增加以及更高的HLA I类和II类表达相关。生存分析显示3号染色体单体性与生存率降低之间存在相关性，并确定3号染色体单体性、睫状体受累和最大基底肿瘤直径为最佳预后标志物。
葡萄膜黑色素瘤中的3号染色体单体性与炎症表型的存在相关，该炎症表型包括高HLA I类和II类表达以及肿瘤浸润巨噬细胞数量增加。在多变量Cox回归分析中，尽管随访时间较短，但3号染色体单体性的存在是转移性疾病和生存的最佳预后标志物之一。
