Tzankov Alexandar, Heiss Simone, Ebner Stephanie, Sterlacci William, Schaefer Georg, Augustin Florian, Fiegl Michael, Dirnhofer Stephan
Institute of Pathology, Medical University of Innsbruck, Innsbruck, Austria.
J Clin Pathol. 2007 May;60(5):476-82. doi: 10.1136/jcp.2006.038661. Epub 2006 Jun 21.
To assess the biological significance of vascular endothelial growth factor (VEGF) A, VEGF receptor (Flk-1) and cyclooxygenase 2 (COX2) expression with respect to microvessel density (MVD), proliferative activity (Ki-67), expression of p53 and clinical presentation in a large cohort of nodal B cell lymphomas.
An immunohistochemical and morphometric study was performed on a validated tissue microarray containing 271 B cell lymphoma specimens, 197 of which included follow-up data. Statistical assessment was done by Pearson's chi(2) test, Spearman's rank correlation coefficient, analysis of variance and survival analysis.
266 (98%) cases were evaluable. Strong VEGF expression was observed in only 20 diffuse large B cell lymphomas (DLBCLs). Flk-1 and COX2 were expressed in 53 and 21 cases, respectively, mainly in DLBCLs, follicular lymphoma (FL) grade 3 and mantle cell lymphomas (MCLs), in a low proportion of cells. MVD decreased in the following order: DLBCLs, FLs, MCLs and small lymphocytic lymphomas/chronic lymphocytic leukaemia (SLL/CLLs). VEGF expression correlated with Ki-67, p53 and COX2 expression in the whole cohort and in DLBCLs. Flk-1 expression correlated with Ki-67 in the cohort and in SLL/CLL and FL grade 1 and 2. COX2 expression correlated with Ki-67 and p53. The analysed angiogenesis parameters did not correlate with clinical parameters or survival.
Angiogenesis plays a differential role in various B cell lymphomas. Aggressive lymphomas express the potential molecular therapeutic targets VEGF and COX2, and have higher MVD. In a few low proliferation-fraction lymphomas, Flk-1 might have a role in proliferative advantage. Therapeutic strategies aimed at angiogenesis should take into account lymphoma heterogeneity.
评估血管内皮生长因子（VEGF）A、VEGF受体（Flk-1）和环氧合酶2（COX2）的表达在大量淋巴结B细胞淋巴瘤患者中与微血管密度（MVD）、增殖活性（Ki-67）、p53表达及临床表现之间的生物学意义。
对一个包含271例B细胞淋巴瘤标本的经过验证的组织芯片进行免疫组织化学和形态学研究，其中197例包含随访数据。采用Pearson卡方检验、Spearman等级相关系数、方差分析和生存分析进行统计学评估。
266例（98%）病例可评估。仅在20例弥漫性大B细胞淋巴瘤（DLBCL）中观察到VEGF强表达。Flk-1和COX2分别在53例和21例中表达，主要在DLBCL、3级滤泡性淋巴瘤（FL）和套细胞淋巴瘤（MCL）中，细胞比例较低。MVD按以下顺序降低：DLBCL、FL、MCL和小淋巴细胞淋巴瘤/慢性淋巴细胞白血病（SLL/CLL）。在整个队列和DLBCL中，VEGF表达与Ki-67、p53和COX2表达相关。在队列以及SLL/CLL和1级及2级FL中，Flk-1表达与Ki-67相关。COX2表达与Ki-67和p53相关。分析的血管生成参数与临床参数或生存无关。
血管生成在各种B细胞淋巴瘤中起不同作用。侵袭性淋巴瘤表达潜在的分子治疗靶点VEGF和COX2，且MVD较高。在少数低增殖分数的淋巴瘤中，Flk-1可能在增殖优势中起作用。针对血管生成的治疗策略应考虑淋巴瘤的异质性。
