Prognostic significance of thrombomodulin expression and vascular invasion in stage I squamous cell carcinoma of the lung

Abstract

Thrombomodulin (TM) is an important modulator of intravascular coagulation. TM exists on endothelial cells and on several types of tumor cells, especially squamous cell carcinoma cells. Tumor cell TM is thought to be associated with progression and metastasis of the tumor. To evaluate the prognostic significance of TM in lung cancer, we examined TM expression and vascular invasion in surgical specimens obtained from 90 patients with completely resected stage I non-small cell lung cancer (NSCLC). In addition, we correlate these pathologic data to other clinicopathologic data, including the outcome of the patients. Squamous cell carcinomas had a significantly higher incidence ( P<0.0001) of TM expression (22/36 cases, 61%) than adenocarcinomas (9/54 cases, 17%). In 36 squamous cell carcinoma patients, both vascular invasion ( P=0.0153; risk ratio 6.507) and TM non-expression ( P=0.0282; risk ratio 3.584) were significant for a poor prognosis. Univariate analysis of patient survival rates also revealed that vascular invasion and TM expression were significant prognostic factors ( P=0.0036 and 0.012, respectively). Further, combination analysis of vascular invasion and TM expression in the squamous cell carcinoma patients showed that the 5-year survival rate was 90% in patients with TM expression and without vascular invasion, but 21% in patients with vascular invasion and without TM expression ( P=0.0004). Since our results suggest that vascular invasion and TM expression are independent prognostic factors of stage I squamous cell carcinoma of the lung, and since the two factors play different roles in the metastatic process of cancers (promotion of metastasis by vascular invasion and inhibition of metastasis by TM expression), the combination evaluation of vascular invasion and TM expression may be very significant in evaluating the prognosis of patients with completely resected stage I squamous cell carcinoma.