Inufusa H, Nakatani Y, Adachi T, Wakano T, Nakajima A, Nakamura M, Suzuki M, Ando O, Kurimoto M, Miyake M, Shindo K, Yasutomi M
The First Department of Surgery, Kinki University School of Medicine, Osaka, 589-8511, Japan.
Int J Oncol. 1998 Sep;13(3):481-7. doi: 10.3892/ijo.13.3.481.
Association between Ley expression and prognosis of breast cancer was investigated using monoclonal antibody (MoAb) FS01, which recognizes Ley as an epitope, inhibits the procoagulant activity of cancer cell-derived coagulating activity 1 (CCA-1). Expression intensity and procoagulant activity of CCA-1, tissue factor and HLA-DR on breast cancer cell lines were also examined. Immunohistochemical staining of Ley was performed on primary lesions of 223 breast cancer patients who received absolute curative operation. Flow cytometric analysis and clot timer was used to detect expression and activity of each procoagulant on cancer cell lines. The Ley expression was 73.5%, and no significant relation was observed between clinicopathological factors and intensity of Ley expression. The group showing strong Ley positivity had a significantly poorer prognosis than the Ley-negative group in 5-year disease-free survival (p=0.019). Multivariate analysis using the Cox's proportional hazards' regression model showed that Ley expression is an independent prognostic factor (p=0.018), following tumor size and lymph node metastasis. Ley expression on cancer cell surface is higher than tissue factor and HLA-DR. FS01 and anti-tissue factor MoAb inhibited the coagulating activity of tissue factor-expressing lines, but no cells were inhibited by staphylococcal enterotoxin A, which is known to inhibit the coagulating activity of HLA-DR. CCA-1 and tissue factor plays a important role in the blood coagulating activity of breast cancer cell lines. Breast cancer patients are thought to have a poor prognosis because Ley expression on the surface of the cancer cell induces blood coagulation via CCA-1.
使用单克隆抗体（MoAb）FS01研究了Ley表达与乳腺癌预后之间的关联，该抗体将Ley识别为一个表位，可抑制癌细胞衍生的凝血活性1（CCA-1）的促凝活性。还检测了乳腺癌细胞系上CCA-1、组织因子和HLA-DR的表达强度及促凝活性。对223例接受根治性手术的乳腺癌患者的原发灶进行了Ley的免疫组织化学染色。采用流式细胞术分析和凝血时间测定仪检测癌细胞系上各促凝剂的表达和活性。Ley表达率为73.5%，临床病理因素与Ley表达强度之间未观察到显著相关性。在5年无病生存率方面，Ley强阳性组的预后明显比Ley阴性组差（p=0.019）。使用Cox比例风险回归模型进行的多因素分析表明，Ley表达是一个独立的预后因素（p=0.018），仅次于肿瘤大小和淋巴结转移。癌细胞表面的Ley表达高于组织因子和HLA-DR。FS01和抗组织因子单克隆抗体抑制了表达组织因子的细胞系的凝血活性，但葡萄球菌肠毒素A（已知可抑制HLA-DR的凝血活性）对细胞无抑制作用。CCA-1和组织因子在乳腺癌细胞系的血液凝固活性中起重要作用。乳腺癌患者被认为预后较差，因为癌细胞表面的Ley表达通过CCA-1诱导血液凝固。
