Department of Ophthalmology, University of Cincinnati College of Medicine, Stetson Building - Suite 5300, 260 Stetson Street, Cincinnati, OH 45267-0527, USA.
Graefes Arch Clin Exp Ophthalmol. 2011 Dec;249(12):1795-803. doi: 10.1007/s00417-011-1769-7. Epub 2011 Aug 17.
To determine the relationship between immunohistochemical reactivity to osteopontin, vimentin, keratin 8/18, LZTS1, and beta-catenin and clinical and histopathological prognostic factors for metastasis and death in archival specimens of primary uveal melanomas, and the prognostic value of the evaluated study variables for death from metastasis.
Retrospective analysis of clinical records and formalin-fixed, paraffin-embedded slides of primary uveal melanomas treated by enucleation during May 1 1999, through June 30 2009. Immunofluorescent staining of each tumor was assessed on newly prepared histologic slides after the application of antibodies directed against five biomarkers associated with unfavorable prognosis in uveal melanoma.
After exclusions, our study group consisted of 82 cases. Immunofluorescence was observed in 40.2% of specimens evaluated for keratin, 50.0% evaluated for osteopontin, 26.8% evaluated for β-catenin, 65.9% evaluated for vimentin, and 70.7% evaluated for LZTS1. Through available follow-up, 27 patients (32.9%) were dead of confirmed or suspected metastatic uveal melanoma. None of the patients whose tumor exhibited strong immunoreactivity to β-catenin died of metastasis. In contrast, patients whose tumor exhibited immunoreactivity of any intensity to LZTS1 were more likely to develop metastasis. In multivariate Cox proportional hazards modeling, a composite variable that took into account the immunostaining for both β-catenin and LZTS1 had a statistically significant relationship with patient's survival time.
Our study suggests that conventional clinical and histopathological prognostic factors, and immunoexpression of β-catenin and LZTS1 combined may allow better prognostication of metastasis than clinical and histomorphological factors alone.
确定免疫组织化学反应与骨桥蛋白、波形蛋白、角蛋白 8/18、LZTS1 和β-连环蛋白之间的关系，以及这些反应与原发性葡萄膜黑色素瘤转移和死亡的临床和组织病理学预后因素之间的关系，以及评估研究变量对转移相关死亡的预后价值。
对 1999 年 5 月 1 日至 2009 年 6 月 30 日期间接受眼球摘除术治疗的原发性葡萄膜黑色素瘤的临床记录和福尔马林固定、石蜡包埋切片进行回顾性分析。在应用针对与葡萄膜黑色素瘤不良预后相关的五种生物标志物的抗体后，对新制备的组织学切片进行免疫荧光染色，评估每个肿瘤的免疫荧光。
排除后，我们的研究组包括 82 例病例。评估的角蛋白标本中 40.2%、评估的骨桥蛋白标本中 50.0%、评估的β-连环蛋白标本中 26.8%、评估的波形蛋白标本中 65.9%和评估的 LZTS1 标本中 70.7%的标本观察到免疫荧光。通过可获得的随访，27 例（32.9%）患者死于确诊或疑似转移性葡萄膜黑色素瘤。β-连环蛋白免疫反应强烈的患者均未死于转移。相比之下，肿瘤免疫反应强度为任何强度的 LZTS1 的患者更有可能发生转移。在多变量 Cox 比例风险模型中，同时考虑β-连环蛋白和 LZTS1 免疫染色的复合变量与患者的生存时间具有统计学显著关系。
我们的研究表明，传统的临床和组织病理学预后因素以及β-连环蛋白和 LZTS1 的免疫表达相结合可能比临床和组织形态学因素单独预测转移的预后更好。
