Department of Pathology, Institut Curie, Paris, France.
University of Paris Réné Descartes Faculty of Medicine, Paris, France.
J Pathol Clin Res. 2018 Oct;4(4):227-240. doi: 10.1002/cjp2.105. Epub 2018 Aug 23.
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.
高达 50%的葡萄膜黑色素瘤（UM）在诊断后 10 年内转移到肝脏，这些转移几乎总是迅速致命。由于肝转移的替代和纤维母细胞型的组织病理学生长模式（HGPs），特别是来自结肠癌和乳腺癌的转移，可能具有重要的生物学和预后信息，因此我们研究了 41 名 UM 患者的 41 个肝转移瘤的 HGP，这些患者来自 2006 年至 2017 年期间。20 名患者接受了眼球摘除术，而 21 名患者接受了放射治疗。通过 array 比较基因组杂交分析发现，25 名（64%）患者为高危（单体 3/8q 获得）；13 名（33%）为中危（M3/8 正常或单体 3/8q 获得）；1 名低危（单体 3/8 正常）。主要的 HGP 在 30 例（73%）中为替代型，在 11 例（27%）中为纤维母细胞型。具有替代型的病例表现出明显的血管共生/血管发生。随着肝转移的发展，只有替代型、最大原发肿瘤直径和 R2（不完全切除）状态预测总生存期（OS；p<0.041、p<0.017、p<0.047）下降。多变量分析显示，只有 HGP（危险比；HR=6.51，p=0.008）和切除状态仍然具有显著意义。在这个肝转移阶段，基因组高危变量没有预后价值。卡方检验显示 HGP 与单体 3 或 8q 获得无关。41 名患者中有 18 名（44%）仍患有疾病，23 名（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中切除的 UM 肝转移瘤的替代和纤维母细胞型 HGP 的频率，以及它们对 UM 患者的潜在重要预后价值，就像在其他实体癌中一样。这些结果可能有助于开发用于监测和治疗 UM 转移患者的影像学相关指标和治疗靶点。
