The biological and prognostic significance of angiotropism in uveal melanoma
The biological and prognostic significance of angiotropism in uveal melanoma
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DOI：
10.1038/labinvest.2017.16
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发表时间：
2017-06-01
影响因子：
5
通讯作者：
Lugassy, Claire
中科院分区：
文献类型：
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作者：
Barnhill, Raymond L.;Ye, Mengliang;Lugassy, Claire
血管趋向性是黑色素瘤细胞沿血管和其他结构向血管外迁移的标志，也是皮肤黑色素瘤的预后因素。由于这种在皮肤黑色素瘤中的生物学和预后重要性，血管趋向性在葡萄膜黑色素瘤（UM）中进行了研究。这项回顾性研究是在一家眼科肿瘤转诊中心进行的，包括了2006-2008年期间89名患者。所有患者均被诊断为脉络膜和/或睫状体的UM。所有患者均行去核治疗以达到预后目的和最终治疗。临床、组织病理学和分子变量包括患者年龄、性别、眼外延伸、肿瘤位置（是否为睫状体）、视神经侵犯、血管偏向性、神经偏向性、黑色素瘤细胞类型、BAP1突变和单体3。血管趋向性被定义为黑色素瘤细胞沿腹腔血管表面排列，在巩膜和/或外膜组织中没有内渗。该研究包括51名女性（57.3%）和38名男性，平均和中位年龄：63岁（范围：25-92岁）。平均随访4.4年（0.2 ~ 11年）。最后一次随访时，53例（59.6%）患者发生转移，48例（53.9%）患者死于转移。其他记录的主要变量为血管增生（43.8%）、眼外扩张（7.9%）、上皮样/混合细胞型（73.1%）、BAP1突变（41.3%）和3号单体（53.6%）。在多变量分析中，眼外扩张、血管趋向性和3号单体可预测转移，而肿瘤直径、上皮样细胞类型、血管趋向性和3号单体可预测死亡。卡方检验证实血管趋向性与转移和死亡有关，但与BAP1突变和3号单体无关。总之，血管增生和单体3是UM转移和死亡的独立预后因素。然而，无论其预后价值如何，血管增生的真正重要性在于其作为另一种转移途径标志的生物学意义。
Angiotropism is a marker of extravascular migration of melanoma cells along vascular and other structures and prognostic factor in cutaneous melanoma. Because of this biological and prognostic importance in cutaneous melanoma, angiotropism was studied in uveal melanoma (UM). This retrospective study performed at a single ocular oncology referral center included 89 patients from the study period 2006-2008. All patients were diagnosed with UM from the choroid and/or ciliary body. All patients underwent enucleation for prognostic purposes and definitive therapy. Clinical, histopathological, and molecular variables included patient age, gender, extraocular extension, tumor location (ciliary body or not), optic nerve invasion, angiotropism, neurotropism, melanoma cell type, BAP1 mutation, and monosomy 3. Angiotropism was defined as melanoma cells arrayed along the abluminal vascular surfaces without intravasation in the sclera and/or episcleral tissue. The study included 51 women (57.3%) and 38 men with mean and median age: 63 years (range: 25-92). Mean follow-up was 4.4 years (range: 0.2 to 11). Fifty-three (59.6%) patients developed metastases and 48 (53.9%) were dead from metastases at last follow-up. Other principal variables recorded were angiotropism in 43.8%, extraocular extension in 7.9%, epithelioid/mixed cell type in 73.1%, BAP1 mutation in 41.3%, and monosomy 3 in 53.6% of cases. On multivariate analysis, extraocular extension, angiotropism, and monosomy 3 were predictive of metastasis, whereas tumor diameter, epithelioid cell type, angiotropism, and monosomy 3 were predictive of death. Chi-square test confirmed an association between angiotropism and metastasis and death but none with BAP1 mutation and monosomy 3. In conclusion, angiotropism and monosomy 3 were independent prognostic factors for both metastases and death in UM. However, irrespective of any prognostic value, the true importance of angiotropism is its biological significance as a marker of an alternative metastatic pathway.