Stefansson Ingunn M, Salvesen Helga B, Akslen Lars A
The Gade Institute, Section for Pathology, University of Bergen, Haukeland University Hospital, Bergen, Norway.
Cancer Res. 2006 Mar 15;66(6):3303-9. doi: 10.1158/0008-5472.CAN-05-1163.
Angiogenesis is essential for tumor growth, invasion, and metastatic spread. Whereas microvessel density (MVD) has been widely used as a measure of tumor-associated angiogenesis, we now wanted to examine the significance of other angiogenic markers, especially vascular proliferation (by Ki-67/factor VIII staining) and the degree of pericyte coverage [by alpha-smooth muscle actin (alpha-SMA)/factor VIII staining], in a large and population-based series of endometrial carcinoma with complete follow-up. Due to limited information on the role of lymphangiogenesis in these tumors, lymphatic vessel density (LVD) by LYVE-1 staining was also determined, as well as selected angiogenic factors [vascular endothelial growth factor (VEGF)-A, VEGF-C, VEGF-D and basic fibroblast growth factor (bFGF)], which could possibly be related to vascular proliferation and lymphangiogenesis. The information on angiogenic phenotype was related to clinicopathologic features and disease progress. Median vascular proliferation, as estimated by vascular proliferation index (VPI), was 3.9% and high VPI was associated with features of aggressive tumors and decreased survival. The prognostic effect of VPI was superior to that of MVD. Presence of pericyte coverage, as estimated by the alpha-SMA index (SMAI), was 35% and low SMAI was significantly associated with vascular invasion by tumor cells and impaired prognosis. Peritumoral lymphatic vessels (LVD-pt) were found in 39.5% of the cases and high LVD-pt was significantly associated with aggressive tumor features and decreased survival. In multivariate survival analysis, only the extent of vascular proliferation had independent prognostic effect, in addition to well-known clinicopathologic factors, whereas MVD did not have significant prognostic value. In conclusion, our study indicates that vascular proliferation is a meaningful variable in assessing the angiogenic phenotype of endometrial carcinoma.
血管生成对于肿瘤的生长、侵袭和转移扩散至关重要。尽管微血管密度（MVD）已被广泛用作肿瘤相关血管生成的指标，但我们现在希望在一个基于人群且有完整随访的大型子宫内膜癌系列研究中，检验其他血管生成标志物的意义，尤其是血管增殖（通过Ki-67/因子VIII染色）和周细胞覆盖程度[通过α-平滑肌肌动蛋白（α-SMA）/因子VIII染色]。由于关于淋巴管生成在这些肿瘤中作用的信息有限，还通过LYVE-1染色测定了淋巴管密度（LVD），以及可能与血管增殖和淋巴管生成相关的选定血管生成因子[血管内皮生长因子（VEGF）-A、VEGF-C、VEGF-D和碱性成纤维细胞生长因子（bFGF）]。血管生成表型的信息与临床病理特征和疾病进展相关。通过血管增殖指数（VPI）估计的血管增殖中位数为3.9%，高VPI与侵袭性肿瘤特征和生存率降低相关。VPI的预后效果优于MVD。通过α-SMA指数（SMAI）估计的周细胞覆盖存在率为35%，低SMAI与肿瘤细胞的血管侵袭和预后受损显著相关。在39.5%的病例中发现了肿瘤周围淋巴管（LVD-pt），高LVD-pt与侵袭性肿瘤特征和生存率降低显著相关。在多变量生存分析中，除了众所周知的临床病理因素外，只有血管增殖程度具有独立的预后作用，而MVD没有显著的预后价值。总之，我们的研究表明血管增殖是评估子宫内膜癌血管生成表型的一个有意义的变量。
