Agnantis N J, Goussia A C, Batistatou A, Stefanou D
Department of Pathology, Medical School, University of Ioannina, 45110 Ioannina, Greece.
In Vivo. 2004 Jul-Aug;18(4):481-8.
The primary determinant of outcome in patients with cancer is the development of distant metastasis. Metastasis is a multistep process involving disruption of cell-matrix adhesion, dissolution of the extracellular matrix, angiogenesis, invasion in the blood vessel wall, extravasation and establishment of a secondary growth. Nowadays, a large number of biochemical and cell biological studies have indicated the important role of extacellular matrix adhesion molecules, proteinases and angiogenic factors in the dissemination of cancer. Cell adhesion molecules, such as integrins, E-cadherin, catenins and CD44 appear to have some prognostic significance, especially in gastric, colorectal and lung cancer patients. Since matrix degrading proteinases are involved in cancer spread, they should be good candidates as prognostic factors. The proteinase which has been investigated in greatest detail is uPA in breast cancer. As a marker of cancer, its main value is to aid in selecting the subgroups of node-negative breast cancer patients that are unlikely to benefit from adjuvant chemotherapy. Cathepsin D and metalloproteinases (MMPs) look promising prognostic markers but further work is needed to establish their utility. Intratumoral angiogenesis is a putative prognostic indicator for some types of cancer. High expression of the angiogenic factor VEGF is associated with angiogenesis and an unfavourable survival.
癌症患者预后的主要决定因素是远处转移的发生。转移是一个多步骤过程,涉及细胞与基质黏附的破坏、细胞外基质的溶解、血管生成、血管壁侵袭、外渗以及继发性生长的建立。如今,大量的生物化学和细胞生物学研究表明,细胞外基质黏附分子、蛋白酶和血管生成因子在癌症扩散中起重要作用。细胞黏附分子,如整合素、E-钙黏蛋白、连环蛋白和CD44似乎具有一定的预后意义,尤其是在胃癌、结直肠癌和肺癌患者中。由于基质降解蛋白酶参与癌症扩散,它们应是良好的预后因素候选者。在乳腺癌中研究最详细的蛋白酶是尿激酶型纤溶酶原激活剂(uPA)。作为一种癌症标志物,其主要价值在于帮助筛选不太可能从辅助化疗中获益的淋巴结阴性乳腺癌患者亚组。组织蛋白酶D和金属蛋白酶(MMPs)看起来是有前景的预后标志物,但需要进一步研究以确定其效用。肿瘤内血管生成是某些类型癌症的一个假定预后指标。血管生成因子血管内皮生长因子(VEGF)的高表达与血管生成及不良生存相关。