Kadkol ShriHari S, Lin Amy Y, Barak Vivian, Kalickman Inna, Leach Lu, Valyi-Nagy Klara, Majumdar Dibyen, Setty Suman, Maniotis Andrew J, Folberg Robert, Pe'er Jacob
Department of Pathology, University of Illinois at Chicago, 60612, USA.
Invest Ophthalmol Vis Sci. 2006 Mar;47(3):802-6. doi: 10.1167/iovs.05-0422.
This was a pilot study conducted to examine the expression of osteopontin in uveal melanoma and to determine whether serum osteopontin can be used in detecting metastatic uveal melanoma.
Osteopontin mRNA was measured in three uveal melanoma cell lines of various invasive potential by real-time PCR. Tissue sections of primary and metastatic uveal melanomas were stained for osteopontin. Serum osteopontin levels were measured by ELISA assays in 15 patients with metastatic uveal melanoma and in 37 patients who were disease-free for at least 10 years after treatment of the primary tumor. Paired serum samples drawn from eight patients before and after development of metastasis were analyzed.
By real-time PCR, highly invasive primary and metastatic uveal melanoma cells expressed 6- and 250-fold excess osteopontin mRNA, respectively, compared with poorly invasive primary uveal melanoma cells. Tissue sections of primary uveal melanomas lacking looping vasculogenic mimicry patterns either did not stain for osteopontin or exhibited weak, diffuse staining. In primary melanomas containing looping vasculogenic mimicry patterns, strong osteopontin staining was detected in the tumor periphery where patterns were located. Diffuse strong expression of osteopontin was detected in eight samples of uveal melanomas metastatic to the liver. Serum osteopontin levels were significantly higher in patients with metastatic uveal melanoma than in patients who had been disease free for at least 10 years after treatment (P = 0.0001) or in age-matched control subjects. Serum osteopontin levels were significantly higher (P = 0.008) after metastasis than before the detection of metastasis in eight patients. When a cutoff of 10 ng/mL was used, the sensitivity and specificity of serum osteopontin in detecting metastatic melanoma was 87.5%, and the area under the receiver operator characteristic curve was 96%.
Osteopontin is expressed diffusely in tissue sections of hepatic metastases from uveal melanoma, and increased serum osteopontin levels correlate with melanoma metastasis to the liver with high specificity and sensitivity.
本研究为一项初步研究，旨在检测骨桥蛋白在葡萄膜黑色素瘤中的表达，并确定血清骨桥蛋白是否可用于检测转移性葡萄膜黑色素瘤。
通过实时聚合酶链反应（PCR）检测三种具有不同侵袭潜能的葡萄膜黑色素瘤细胞系中的骨桥蛋白信使核糖核酸（mRNA）。对原发性和转移性葡萄膜黑色素瘤的组织切片进行骨桥蛋白染色。采用酶联免疫吸附测定（ELISA）法检测15例转移性葡萄膜黑色素瘤患者及37例原发性肿瘤治疗后至少10年无疾病复发患者的血清骨桥蛋白水平。分析了8例患者转移前后采集的配对血清样本。
通过实时PCR检测，与低侵袭性原发性葡萄膜黑色素瘤细胞相比，高侵袭性原发性和转移性葡萄膜黑色素瘤细胞分别过量表达6倍和250倍的骨桥蛋白mRNA。缺乏环状血管生成拟态模式的原发性葡萄膜黑色素瘤组织切片要么未检测到骨桥蛋白染色，要么显示出微弱、弥漫性染色。在含有环状血管生成拟态模式的原发性黑色素瘤中，在模式所在的肿瘤周边检测到强骨桥蛋白染色。在8例转移至肝脏的葡萄膜黑色素瘤样本中检测到骨桥蛋白的弥漫性强表达。转移性葡萄膜黑色素瘤患者的血清骨桥蛋白水平显著高于原发性肿瘤治疗后至少10年无疾病复发患者（P = 0.0001）或年龄匹配的对照受试者。8例患者转移后的血清骨桥蛋白水平显著高于转移检测前（P = 0.008）。当采用10 ng/mL的临界值时，血清骨桥蛋白检测转移性黑色素瘤的敏感性和特异性为87.5%，受试者操作特征曲线下面积为96%。
骨桥蛋白在葡萄膜黑色素瘤肝转移组织切片中弥漫性表达，血清骨桥蛋白水平升高与黑色素瘤肝转移具有高度特异性和敏感性相关。
