Department of Oncology, Danish Colorectal Cancer Group South, Vejle Hospital, Kabbeltoft 25, 7100, Vejle, Denmark.
Virchows Arch. 2010 Mar;456(3):251-60. doi: 10.1007/s00428-009-0878-8. Epub 2010 Feb 9.
The measurement of microvessel density (MVD) is a widely accepted method for assessing the neoangiogenetic activity in neoplasia. The aim of the present study was to compare MVD with single nucleotide polymorphisms (SNPs) in the vascular endothelial growth factor receptor (VEGFR)-1 and VEGFR-2 genes and, furthermore, with quantitative measurements of the receptors in colorectal cancer (CRC) tissue. Prognosis was also assessed. Blood and tissue were collected from 110 patients surgically resected for CRC. SNPs were analysed from genomic DNA by polymerase chain reaction. MVD was assessed by immunohistochemistry using CD34 and CD105 combined with caldesmon in order to identify also immature vessels. Microvessels were counted in three fields of vision, and the mean MVD was used for statistical analysis. The VEGFR-2 1192 C/T and -604 T/C SNPs were associated with the MVD assessed by CD105. The median MVD score for the 1192 CC genotype was significantly lower compared to the CT + TT genotypes (p = 0.002). The median MVD score for the -604 CC genotype was significantly higher compared to the TT + TC genotypes (p = 0.009). A possible association, although non-significant, was demonstrated for the CD34-positive microvessels. The 1192 CC genotype and the -604 TT + TC genotypes correlated with improved survival. This is the first report on correlations between SNPs in the VEGF receptor genes and MVD in patients with CRC. Associations were shown between two SNPs in the VEGFR-2 gene and the CD105-positive microvessels indicating an impact on neoangiogenesis. Moreover, an association between the SNPs and survival was demonstrated. The clinical implications of these findings need further investigations.
微血管密度 (MVD) 的测量是评估肿瘤新生血管活性的一种广泛接受的方法。本研究的目的是比较 MVD 与血管内皮生长因子受体 (VEGFR)-1 和 VEGFR-2 基因中的单核苷酸多态性 (SNP)，并进一步与结直肠癌 (CRC) 组织中受体的定量测量进行比较。还评估了预后。从 110 名接受 CRC 手术切除的患者中采集血液和组织。通过聚合酶链反应从基因组 DNA 中分析 SNP。通过免疫组织化学使用 CD34 和 CD105 联合 caldesmon 评估 MVD，以鉴定不成熟的血管。在三个视野中计数微血管，并使用平均 MVD 进行统计分析。CD105 评估的 MVD 与 VEGFR-2 1192 C/T 和 -604 T/C SNP 相关。1192 CC 基因型的中位数 MVD 评分明显低于 CT + TT 基因型（p = 0.002）。-604 CC 基因型的中位数 MVD 评分明显高于 TT + TC 基因型（p = 0.009）。虽然没有统计学意义，但 CD34 阳性微血管显示出可能的相关性。1192 CC 基因型和-604 TT + TC 基因型与生存改善相关。这是第一个关于 CRC 患者 VEGF 受体基因 SNP 与 MVD 之间相关性的报告。在 VEGFR-2 基因的两个 SNP 与 CD105 阳性微血管之间显示出相关性，表明对新生血管生成有影响。此外，还证明了 SNP 与生存之间的关联。这些发现的临床意义需要进一步研究。
