Duffy M J
Nuclear Medicine Department, St. Vincent's Hospital, Dublin 4, Ireland.
Clin Cancer Res. 1996 Apr;2(4):613-8.
It is the ability to invade and metastasize that ultimately determines the prognosis in cancer. Comprising one of the key groups of molecules involved in invasion and metastasis are proteases such as urokinase plasminogen activator and cathepsins B, D, and L, as well as various metalloproteases. These proteases catalyze degradation of the interstitial matrix and basement membranes, allowing cancer cells to invade locally and metastasize to distant sites. If proteases are directly and causally involved in cancer spread, they have the potential to be new prognostic markers in cancer. One of the best examples of a correlation between high levels of a protease in a primary tumor and poor prognosis is urokinase plasminogen activation in breast cancer. In this malignancy, the urokinase plasminogen activator is a strong and independent prognostic marker and may be a marker for axillary node-negative disease. The urokinase plasminogen activator may also be a prognostic marker in other cancers such as gastric, colorectal, lung, bladder, cervical, and ovarian cancers. In a number of studies, cathepsin D has been shown to be a prognostic factor in breast cancer. However, results with cathepsin D, especially when immunocytochemistry is used for its detection, are conflicting. Levels of cathepsin B, cathepsin L, and certain metalloproteases may also supply prognostic data in certain cancers, but results with these proteases are still preliminary.
正是侵袭和转移能力最终决定了癌症的预后。参与侵袭和转移的关键分子组之一包括蛋白酶，如尿激酶型纤溶酶原激活剂和组织蛋白酶B、D和L，以及各种金属蛋白酶。这些蛋白酶催化细胞外基质和基底膜的降解，使癌细胞能够局部侵袭并转移至远处部位。如果蛋白酶直接且因果性地参与癌症扩散，它们就有可能成为癌症新的预后标志物。原发性肿瘤中蛋白酶水平高与预后不良之间存在关联的最佳例子之一是乳腺癌中的尿激酶型纤溶酶原激活。在这种恶性肿瘤中，尿激酶型纤溶酶原激活剂是一个强有力的独立预后标志物，可能是腋窝淋巴结阴性疾病的标志物。尿激酶型纤溶酶原激活剂也可能是其他癌症如胃癌、结直肠癌、肺癌、膀胱癌、宫颈癌和卵巢癌的预后标志物。在多项研究中，组织蛋白酶D已被证明是乳腺癌的一个预后因素。然而，关于组织蛋白酶D的结果，尤其是当使用免疫细胞化学检测时，存在矛盾。组织蛋白酶B、组织蛋白酶L和某些金属蛋白酶的水平在某些癌症中也可能提供预后数据，但这些蛋白酶的结果仍属初步。
