Franco Renato, Botti Gerardo, Mascolo Massimo, Loquercio Giovanna, Liguori Giuseppina, Ilardi Gennaro, Losito Simona, La Mura Anna, Calemma Rosa, Ierano Caterina, Bryce Jane, D'Alterio Crescenzo, Scala Stefania
Pathology Department, National Cancer Institute G Pascale, Naples, Italy.
Front Biosci (Elite Ed). 2010 Jan 1;2(1):13-21. doi: 10.2741/e60.
Despite improvements in early diagnosis of uveal melanoma, prognosis is still poor due to metastases development. Neoangiogenesis and migration are requisites to metastasis promotion. Cross-talking between CXCR4-CXCL12 axis and the VEGF pathway was shown to favours tumour progression. CXCR4-CXCL12-VEGF expression was evaluated by immunohistochemistry in 53 selected cases of primary uveal melanoma and in liver melanoma metastases. CXCR4 protein was detected in 41.4 per cent cases, CXCL12 in 43.4 per cent cases and VEGF expression in 39.6 per cent cases. A significant correlation was found between CXCR4 and VEGF expression (p=0.011), CXCL12 and both tumour dimension and (p=0.006) and epithelioid-mixed cytotype (p=0.012). The two cases of uveal melanoma liver metastases in our series showed CXCR4 expression, weak immunoreactivity for CXCL12 and absent VEGF immunostaining. These data indicate that CXCR4-CXCL12 axis and its cross-talking with VEGF plays a role in uveal melanoma metastases and may be new prognostic markers in UMM. Moreover, these results suggest that targeted inhibition of CXCR4 could be introduced to control metastasis development in UMM.
尽管葡萄膜黑色素瘤的早期诊断有所改善,但由于转移的发生,预后仍然很差。新生血管形成和迁移是促进转移的必要条件。CXCR4-CXCL12轴与VEGF途径之间的相互作用被证明有利于肿瘤进展。通过免疫组织化学对53例原发性葡萄膜黑色素瘤及肝黑色素瘤转移病例的CXCR4-CXCL12-VEGF表达进行评估。41.4%的病例检测到CXCR4蛋白,43.4%的病例检测到CXCL12,39.6%的病例检测到VEGF表达。发现CXCR4与VEGF表达之间存在显著相关性(p=0.011),CXCL12与肿瘤大小(p=0.006)及上皮样-混合细胞类型(p=0.012)之间存在显著相关性。我们系列中的两例葡萄膜黑色素瘤肝转移病例显示CXCR4表达、CXCL12弱阳性免疫反应及VEGF免疫染色阴性。这些数据表明,CXCR4-CXCL12轴及其与VEGF的相互作用在葡萄膜黑色素瘤转移中起作用,可能是葡萄膜黑色素瘤新的预后标志物。此外,这些结果表明,可以引入CXCR4的靶向抑制来控制葡萄膜黑色素瘤转移的发生。