Life and Health Sciences Research Institute, ICVS, School of Health Sciences, University of Minho, and Pathology Department, Braga Hospital, 4710-057 Braga, Portugal.
Cancer Genomics Proteomics. 2013 Mar-Apr;10(2):55-67.
Colorectal cancer (CRC) is the third most common type of cancer and the fourth most frequent cause of cancer death. Literature indicates that vascular endothelial growth factor is a predominant angiogenic factor and that angiogenesis plays an important role in the progression of CRC.
The present series consisted of tissue samples obtained from 672 patients who had undergone large bowel resection between 2005 and 2010 at the Braga Hospital, Portugal. Archival paraffin-embedded CRC tissue and normal adjacent samples were used to build up tissue microarray blocks and VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression was immunohistochemically assessed.
We observed an overexpression of VEGF-C in CRC when tumour cells and normal-adjacent tissue were compared (p=0.004). In tumour samples, VEGF-C-positive cases were associated with VEGFR-3 expression (p=0.047). When assessing the correlation between VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expressions and the clinicopathological data, it was revealed that VEGF-A positive cases were associated with male gender (p=0.016) and well-differentiated tumours (p=0.001); VEGF-C with colon cancers (p=0.037), exophytic (p=0.048), moderately-differentiated (p=0.007) and T3/T4 (p=0.010) tumours; VEGFR-2 with invasive adenocarcinoma (p=0.007) and VEGFR-3 with the presence of hepatic metastasis (p=0.032). Overall survival curves for CRC were statistically significant for rectal cancer, VEGF-C expression and stage III (p=0.019) and VEGFR-3 expression and stage IV (p=0.047).
Quantification of VEGF-A, VEGF-C, VEGFR-2 and VEGFR-3 expression seems to provide valuable prognostic information in CRC and the correlation with clinicopathological data revealed an association with characteristics that contribute to progression, invasion and metastasis leading to poorer survival rates and prognosis.
结直肠癌（CRC）是第三大常见癌症，也是第四大常见癌症死亡原因。文献表明，血管内皮生长因子是主要的血管生成因子，血管生成在 CRC 的进展中起着重要作用。
本研究系列包括 2005 年至 2010 年期间在葡萄牙布拉加医院接受大肠切除术的 672 名患者的组织样本。使用存档的石蜡包埋 CRC 组织和正常相邻样本构建组织微阵列块，并通过免疫组织化学评估 VEGF-A、VEGF-C、VEGFR-2 和 VEGFR-3 的表达。
当比较肿瘤细胞和正常相邻组织时，我们观察到 CRC 中 VEGF-C 的过度表达（p=0.004）。在肿瘤样本中，VEGF-C 阳性病例与 VEGFR-3 表达相关（p=0.047）。在评估 VEGF-A、VEGF-C、VEGFR-2 和 VEGFR-3 表达与临床病理数据之间的相关性时，发现 VEGF-A 阳性病例与男性性别（p=0.016）和分化良好的肿瘤（p=0.001）相关；VEGF-C 与结肠癌（p=0.037）、外生性（p=0.048）、中度分化（p=0.007）和 T3/T4（p=0.010）肿瘤相关；VEGFR-2 与浸润性腺癌（p=0.007）相关，而 VEGFR-3 与肝转移存在相关（p=0.032）。CRC 的总生存曲线在直肠癌、VEGF-C 表达和 III 期（p=0.019）以及 VEGFR-3 表达和 IV 期（p=0.047）方面具有统计学意义。
定量评估 VEGF-A、VEGF-C、VEGFR-2 和 VEGFR-3 的表达似乎为 CRC 提供了有价值的预后信息，并且与临床病理数据的相关性表明与促进进展、侵袭和转移的特征相关，从而导致生存率和预后较差。
