PDF(Pubmed)
Abstract：
Up to 50% of uveal melanomas (UM) metastasise to the liver within 10 years of diagnosis, and these almost always prove rapidly fatal. As histopathological growth patterns (HGPs) of liver metastases of the replacement and desmoplastic type, particularly from colon and breast carcinoma, may import valuable biological and prognostic information, we have studied HGP in a series of 41 UM liver metastases originating from 41 patients from the period 2006-2017. Twenty patients underwent enucleation while 21 had radiation therapy. Analysis of UM by array comparative genomic hybridisation revealed: 25 (64%) patients with high risk (monosomy3/8q gain); 13 (33%) intermediate risk (M3/8normal or disomy3/8q gain); and 1 low risk (disomy3/8normal). The principal HGP was replacement in 30 (73%) cases and desmoplastic in 11 (27%) cases. Cases with replacement demonstrated striking vascular co-option/angiotropism. With the development of liver metastasis, only the replacement pattern, largest primary tumour diameter, and R2 (incomplete resection) status predicted diminished overall survival (OS; p < 0.041, p < 0.017, p < 0.047, respectively). On multivariate analysis, only HGP (hazard ratio; HR = 6.51, p = 0.008) and resection status remained significant. The genomic high-risk variable had no prognostic value at this stage of liver metastasis. Chi-square test showed no association of HGP with monosomy 3 or 8q gain. Eighteen of 41 (44%) patients are alive with disease and 23 (56%) patients died with follow-up ranging from 12 to 318 months (mean: 70 months, median: 47 months). In conclusion, we report for the first time the frequency of the replacement and desmoplastic HGPs in liver UM metastases resected from living patients, and their potential important prognostic value for UM patients, as in other solid cancers. These results may potentially be utilised to develop radiological correlates and therapeutic targets for following and treating patients with UM metastases.
摘要：
高达50％的葡萄膜黑色素瘤（UM）在诊断后10年内转移到肝脏，这些几乎总是被证明是致命的。作为替代和增生型肝转移的组织病理学生长模式（HGPs），特别是结肠癌和乳腺癌，可能导入有价值的生物学和预后信息，我们研究了2006-2017年期间41例源于41例患者的一系列UM肝转移瘤中的HGP.20例患者接受了摘除，而21例接受了放射治疗。通过阵列比较基因组杂交对UM进行分析显示：25例（64％）具有高风险（单3/8q增益）的患者；13例（33％）中等风险（M3/8normal或dismy3/8q增益）；和1个低风险（dismy3/8normal）。主要HGP在30例（73％）中被替换，在11例（27％）中被增生。置换病例表现出明显的血管协同选择/血管生成。随着肝转移的发展，只有替换模式，最大的原发性肿瘤直径，和R2(不完全切除)状态预测总生存期减少(OS;分别为p<0.041,p<0.017,p<0.047)。在多变量分析中，只有HGP(风险比;HR=6.51,p=0.008)和切除状态仍然显著.基因组高危变量在肝转移的这一阶段没有预后价值。卡方检验显示HGP与3号或8q增益无相关性。41例患者中有18例（44％）患有疾病，23例（56％）患者死亡，随访时间为12至318个月（平均：70个月，中位数：47个月）。总之,我们首次报道了从活体患者切除的肝UM转移灶中置换和促纤维化HGPs的频率，以及它们对UM患者潜在的重要预后价值，和其他实体癌一样。这些结果可能被用于开发放射学相关性和治疗靶标，以跟踪和治疗UM转移患者。
