Damato Bertil, Duke Catherine, Coupland Sarah E, Hiscott Paul, Smith Peter A, Campbell Ian, Douglas Angela, Howard Peter
Ocular Oncology Service, Royal Liverpool University Hospital, Liverpool, United Kingdom.
Ophthalmology. 2007 Oct;114(10):1925-31. doi: 10.1016/j.ophtha.2007.06.012. Epub 2007 Aug 27.
Chromosome 3 loss and chromosome 8 gains in uveal melanoma are associated with metastatic death. Since 1999, we have offered cytogenetic analysis to patients treated by local resection or enucleation. This study correlated our cytogenetic results with clinical and histologic predictors and disease-specific mortality.
Nonrandomized case series.
Three hundred fifty-six patients with uveal melanoma with data on chromosome 3 and chromosome 8.
Tumor diameter was measured by echography. Cell type, presence of closed connective tissue loops, and mitotic rate were determined histopathologically. Fluorescence in-situ hybridization was performed using centromeric probes for chromosomes 3 and 8 and for c-myc. Patients were flagged at the National Health Service Cancer Registry, which notified us of any deaths. Statistics included Cox multivariate analysis and Kaplan-Meier analysis.
Disease-specific mortality, according to clinical, histologic and cytogenetic features as well as correlation between cytogenetic variables and other mortality predictors, including a predictive index.
The patients had a mean age of 61.9 years. The tumors showed no cytogenetic abnormalities of chromosomes 3 or 8 in 42%, chromosome 8 gains in 11%, monosomy 3 in 21%, and both abnormalities in 27%. These correlated with ciliary body involvement (P<0.001), extraocular spread (P = 0.007), large basal tumor diameter (P<0.001), epithelioid cellularity (P<0.001), closed connective tissue loops (P<0.001), and mitotic rate exceeding 4/40 high power fields (P<0.001). By the study close, 76 patients had died (67 from metastasis). Cox multivariate analysis showed the most significant factors to be basal tumor diameter (P<0.001), monosomy 3 (P<0.001), and epithelioid cellularity (P = 0.004). A predictive index (PI) was derived from these variables. Kaplan-Meier analysis showed that 5-year metastatic death rates ranged from 0% in 84 patients with low-grade melanoma (PI<19) to 66% in 100 patients with high-grade tumor (PI>26; 95% confidence interval, 53%-80%).
Cytogenetic analysis of chromosomes 3 and 8 enhances prediction of disease-specific mortality after treatment of uveal melanoma but must be interpreted together with tumor diameter and cell type.
葡萄膜黑色素瘤中3号染色体缺失和8号染色体增加与转移性死亡相关。自1999年以来，我们为接受局部切除或眼球摘除术治疗的患者提供细胞遗传学分析。本研究将我们的细胞遗传学结果与临床、组织学预测指标及疾病特异性死亡率进行关联。
非随机病例系列。
356例有3号和8号染色体数据的葡萄膜黑色素瘤患者。
通过超声检查测量肿瘤直径。组织病理学确定细胞类型、闭合结缔组织环的存在情况及有丝分裂率。使用针对3号和8号染色体以及c-myc的着丝粒探针进行荧光原位杂交。患者在国家医疗服务体系癌症登记处进行标记，登记处会通知我们任何死亡情况。统计分析包括Cox多变量分析和Kaplan-Meier分析。
根据临床、组织学和细胞遗传学特征的疾病特异性死亡率，以及细胞遗传学变量与其他死亡率预测指标之间的相关性，包括一个预测指数。
患者的平均年龄为61.9岁。42%的肿瘤未显示3号或8号染色体的细胞遗传学异常，11%有8号染色体增加，21%有3号染色体单体性，27%有两种异常。这些与睫状体受累（P<0.001）、眼外扩散（P = 0.007）、基底肿瘤直径大（P<0.001）、上皮样细胞性（P<0.001）、闭合结缔组织环（P<0.001）以及有丝分裂率超过4/40高倍视野（P<0.001）相关。到研究结束时，76例患者死亡（67例死于转移）。Cox多变量分析显示最显著的因素是基底肿瘤直径（P<0.001）、3号染色体单体性（P<0.001）和上皮样细胞性（P = 0.004）。从这些变量得出一个预测指数（PI）。Kaplan-Meier分析显示，5年转移性死亡率在84例低级别黑色素瘤患者（PI<19）中为0%，在100例高级别肿瘤患者（PI>26；95%置信区间，53%-80%）中为66%。
对3号和8号染色体进行细胞遗传学分析可增强葡萄膜黑色素瘤治疗后疾病特异性死亡率的预测，但必须结合肿瘤直径和细胞类型进行解读。
