An immunohistochemical study of thrombomodulin in oral squamous cell carcinoma and its association with invasive and metastatic potential

Thrombomodulin (TM) is a glycoprotein that was originally identified on vascular endothelium and characterized as a natural endothelial anticoagulant. We reported previously that TM was also expressed at cell-cell boundaries of squamous epithelium, except in the basal layer cells and upper granular layer cells. The expression pattern of TM in the squamous cells implies that this molecule might be associated with keratinocyte differentiation, as well as being a potent anticoagulant. In the present study we examined TM expression immunohistochemically in biopsy specimens from 65 patients with primary oral squamous cell carcinoma (OSCC), and compared the results with the biological behavior of the carcinomas. The patients with intense TM expression in the carcinoma showed a significantly lower frequency of lymph node metastasis and significantly more favorable survival than those with negative TM expression. The TM expression was a better marker than the other prognostic factors, such as differentiation degree, tumor size and invasion mode. When TM expression was compared between the primary and metastatic lesions in the 36 patients who had lymph node metastasis, 14 (39%) showed decreased TM expression, 19 (53%) showed no change, and 3 (8%) showed an increase in the metastatic lesions. Wilcoxon's signed-rank test indicated that tumor cells positive for TM expression were significantly rarer in the metastatic lesions than in the primary tumors (P < 0.05). These results indicate that reduced expression of TM is associated with metastasis of carcinoma cells. The reduction of TM expression seems to play an important role in the metastatic process of OSCC, and to be related with a poor outcome for the patients.