Citak Elvan Caglar, Oguz Aynur, Karadeniz Ceyda, Akyurek Nalan
Department of Pediatric Oncology, Faculty of Medicine, Gazi University, Huseyin Onat Sokak, No. 15/13, Asagiayranci, Ankara 06510, Turkey.
Pathol Res Pract. 2008;204(2):89-96. doi: 10.1016/j.prp.2007.11.005. Epub 2008 Jan 18.
This immunohistochemical study was carried out to evaluate the role of vascular endothelial growth factor (VEGF), matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9), their inhibitor (tissue inhibitor of metalloproteinase-1, TIMP-1), and microvessel density (MVD) in the clinicopathologic behavior of childhood Hodgkin's lymphoma (HL). Paraffin-embedded histologic sections from 15 children with HL were immunohistochemically stained with MMP-2, MMP-9, TIMP-1, VEGF, and CD31 antibodies to investigate the correlation between the expression of these markers and the clinicopathologic characteristics of HL. Expression of MMP-2 and VEGF in Hodgkin and Reed-Sternberg cells (HRS) was more frequent in nodular sclerosis than in other subtypes (p=0.07 and 0.08, respectively). None of the study parameters in HRS cell were associated with age, sex, disease stage, extranodal disease, and the occurrence of bulky tumor. There was a trend toward advanced stage in negative TIMP-1 staining in HRS cells (p=0.06). In reactive lymphocytes, MMP-2 expression was correlated with MVD (r=0.68, p=0.005), and MMP-9 expression was correlated with B symptoms (p=0.003). Also, low TIMP-1 expression in reactive lymphocytes was frequently found in patients with advanced stage (p=0.048). There was a positive correlation with the ratio of MMP-2 expression in reactive lymphocytes and MVD (r=0.68, p=0.005). Expression of MMP-9 in reactive lymphocytes was correlated with MVD without statistical significance (r=0.487, p=0.06). Our results suggest that, as in many solid tumors, angiogenesis and angiogenic factors may play an important role in childhood HL. Larger series of patients are needed to determine the prognostic value of angiogenesis in childhood HL.
本免疫组化研究旨在评估血管内皮生长因子（VEGF）、基质金属蛋白酶-2和-9（MMP-2和MMP-9）、其抑制剂（金属蛋白酶组织抑制剂-1，TIMP-1）以及微血管密度（MVD）在儿童霍奇金淋巴瘤（HL）临床病理行为中的作用。对15例HL患儿的石蜡包埋组织切片进行免疫组化染色，使用MMP-2、MMP-9、TIMP-1、VEGF和CD31抗体，以研究这些标志物的表达与HL临床病理特征之间的相关性。在结节硬化型中，霍奇金和里德-斯腾伯格细胞（HRS）中MMP-2和VEGF的表达比其他亚型更常见（分别为p = 0.07和0.08）。HRS细胞中的研究参数均与年龄、性别、疾病分期、结外疾病和巨大肿瘤的发生无关。HRS细胞中TIMP-1染色阴性有进展期的趋势（p = 0.06）。在反应性淋巴细胞中，MMP-2表达与MVD相关（r = 0.68，p = 0.005），MMP-9表达与B症状相关（p = 0.003）。此外，进展期患者反应性淋巴细胞中TIMP-1表达低的情况较为常见（p = 0.048）。反应性淋巴细胞中MMP-2表达比例与MVD呈正相关（r = 0.68，p = 0.005）。反应性淋巴细胞中MMP-9表达与MVD相关，但无统计学意义（r = 0.487，p = 0.06）。我们的结果表明，与许多实体瘤一样，血管生成和血管生成因子可能在儿童HL中起重要作用。需要更大规模的患者系列研究来确定血管生成在儿童HL中的预后价值。
