Expression of thrombomodulin in squamous cell carcinoma of the lung: its relationship to lymph node metastasis and prognosis of the patients

Thrombomodulin (TM) is a type of thrombin receptor that was identified orig inally on the endothelium and acts as a natural anticoagulant through conve rting thrombin from a procoagulant protease to an anticoagulant. We reporte d previously that TM was also expressed in the squamous epithelium mainly a t the intercellular bridges. In this study, we examined TM expression in th e primary lesions of 81 patients with squamous cell carcinomas (SCCs) of th e lung and in the lymph node metastatic lesions of 39 patients using immuno histochemical methods. The carcinoma tissues expressed TM mainly at the cel l-cell boundaries and also in the cytoplasm. When TM expression was compare d between the primary and metastatic lesions in the 39 patients who had lym ph node metastasis, 26 (67%) showed decreased TM expression, 13 (33%) showe d no change, and none (0%) showed an increase in the metastatic lesions. Wi lcoxon's signed-rank test indicated that tumor cells that were positive for TM expression were significantly rarer in the metastatic lesions than in t he primary tumors (P < 0.0001). The present study also showed that the pati ents with TM-negative expression in the primary tumors showed significantly poorer survival than those with TM-positive expression, mainly due to dist ant metastases of poorly-differentiated SCCs with negative TM expression in the primary tumors. These results indicate that the reduction of TM expres sion seems to play an important role in the metastatic process of lung SCCs , (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.