Hillen Femke, van de Winkel Anouk, Creytens David, Vermeulen Anton H M, Griffioen Arjan W
Angiogenesis Laboratory, Research Institute for Growth and Development (GROW), Department of Pathology, University Hospital Maastricht, Maastricht, The Netherlands.
Melanoma Res. 2006 Oct;16(5):453-7. doi: 10.1097/01.cmr.0000232291.68666.4c.
The induction of angiogenesis is crucial in the development of most human tumors. Angiogenesis is routinely assessed by the density of tumor microvessels. This technique reveals controversial results on the clinical and prognostic value of angiogenesis in melanoma. We investigated angiogenesis in tumor tissues of 58 cutaneous melanoma patients, of which a clinical follow-up of over 10 years was available, through assessment of microvessel density and by enumeration of the number of proliferating endothelial cells. To that end, vessels were immunohistochemically detected by CD31/CD34 staining, and proliferating endothelial cells were enumerated in a double staining with the proliferation marker Ki67. We found that microvessel density did not correlate with tumor stage or survival, neither in intratumoral nor in peritumoral areas. In contrast, proliferating endothelial cells were only observed in intratumoral areas and were correlated positively with tumor stage and the presence of distant metastases. In addition, a strong positive correlation was found with the number of proliferating tumor cells. Finally, high numbers of growing endothelial cells predicted short survival. Our results show that angiogenesis could best be measured by enumeration of proliferating endothelial cells and that this parameter has prognostic value in patients with cutaneous melanoma.
血管生成的诱导在大多数人类肿瘤的发展中至关重要。血管生成通常通过肿瘤微血管密度来评估。这项技术在黑色素瘤血管生成的临床和预后价值方面显示出有争议的结果。我们通过评估微血管密度和计数增殖内皮细胞的数量，对58例皮肤黑色素瘤患者的肿瘤组织中的血管生成进行了研究，其中有超过10年的临床随访数据。为此，通过CD31/CD34染色对血管进行免疫组织化学检测，并在与增殖标记物Ki67的双重染色中对增殖内皮细胞进行计数。我们发现，无论是在肿瘤内还是肿瘤周围区域，微血管密度均与肿瘤分期或生存率无关。相比之下，增殖内皮细胞仅在肿瘤内区域观察到，并且与肿瘤分期和远处转移的存在呈正相关。此外，与增殖肿瘤细胞的数量呈强正相关。最后，大量生长的内皮细胞预示着生存期短。我们的结果表明，通过计数增殖内皮细胞来测量血管生成最为合适，并且该参数对皮肤黑色素瘤患者具有预后价值。
