Division of Pathology, School of Cancer Studies, University of Liverpool, Department of Medical Physics and Clinical Engineering, Royal Liverpool University Hospital, Liverpool, UK.
Acta Ophthalmol. 2012 Sep;90(6):534-9. doi: 10.1111/j.1755-3768.2010.02038.x. Epub 2010 Nov 26.
Almost 40% of uveal melanomas (UM) are fatal, because of metastatic disease that usually involves the liver. Partial or complete deletion of chromosome 3 (i.e., monosomy 3) is a strong predictor of metastatic mortality; however, genetic analysis is not always possible. The aim of this study was to determine whether heat shock protein 27 (HSP-27) protein expression could reliably predict prognosis.
Immunohistochemical analysis of HSP-27 protein expression was performed on formalin-fixed, paraffin-embedded sections from 99 UM of known chromosome 3 status, as determined by multiplex ligation-dependent probe amplification. Slides were evaluated blind by three independent observers. The percentage of tumour cells staining for HSP-27 was categorized as: 0 (<1%); 1 (1-24%); 2 (25-49%); 3 (50-74%) or 4 (>74%). The staining intensity was categorized as: 0 (no staining); 1 (weak); 2 (moderate) and 3 (strong). These two categories were multiplied together to obtain the HSP-27 expression score. All data were processed in spss for statistical analyses.
Heat shock protein 27 score was lower in monosomy 3 melanomas than in disomy 3 tumours (p<0.001; Mann-Whitney U-test). An 'accelerated failure time model' was used to generate predicted survival for all patients included in the study. Kaplan-Meier analysis indicated a significantly decreased predicted 8-year survival rate for patients with an HSP-27 Score≤6 (p=0.03; Log rank test). Predicting monosomy 3 was enhanced by considering the HSP-27 score together with basal tumour diameter, melanoma cytomorphology and mitotic rate.
Low HSP-27 expression correlates with monosomy 3 in UM and with increased predicted mortality. When assessed together with other clinical and pathological variables, the HSP-27 score enhances estimation of survival probability.
近 40%的葡萄膜黑色素瘤（UM）是致命的，因为转移疾病通常涉及肝脏。染色体 3 的部分或完全缺失（即单体 3）是转移死亡率的强烈预测指标；然而，并非总是可以进行基因分析。本研究旨在确定热休克蛋白 27（HSP-27）蛋白表达是否可可靠地预测预后。
对通过多重连接依赖性探针扩增确定的已知染色体 3 状态的 99 例 UM 的福尔马林固定、石蜡包埋切片进行 HSP-27 蛋白表达的免疫组织化学分析。由三位独立观察者进行盲法评估。肿瘤细胞 HSP-27 染色的百分比分为：0（<1%）；1（1-24%）；2（25-49%）；3（50-74%）或 4（>74%）。染色强度分为：0（无染色）；1（弱）；2（中度）和 3（强）。将这两个类别相乘以获得 HSP-27 表达评分。所有数据均在 spss 中进行统计分析。
单体 3 黑色素瘤的 HSP-27 评分低于二倍体 3 肿瘤（p<0.001；Mann-Whitney U 检验）。使用“加速失效时间模型”为研究中纳入的所有患者生成预测生存率。Kaplan-Meier 分析表明，HSP-27 评分≤6 的患者预测 8 年生存率显著降低（p=0.03；对数秩检验）。当考虑 HSP-27 评分与基础肿瘤直径、黑色素瘤细胞形态学和有丝分裂率一起考虑时，单体 3 的预测得到了增强。
低 HSP-27 表达与 UM 中的单体 3 相关，并与预测死亡率增加相关。当与其他临床和病理变量一起评估时，HSP-27 评分增强了对生存率的估计。
