Anaplastic lymphoma kinase rearrangement may increase the incidence of venous thromboembolism by increasing tissue factor expression in advanced lung adenocarcinoma

BACKGROUND: Patients with lung cancer are at an increased risk for venous thromboembolism (VTE). Approximately 8–15% of patients with advanced non-small-cell lung cancer (NSCLC) experience a VTE throughout the course of the disease. However, the incidence of VTE in different NSCLC molecular subtypes is rarely reported, although there are significant differences in clinical feature and prognosis. Tissue factor (TF) expressed in many solid tumors could trigger the downstream coagulation cascade and lead to thrombin generation and clot formation. METHODS: In the present study, retrospective data were obtained from electronic medical records at Henan Cancer Hospital in China between January 2015 and January 2017. Advanced lung adenocarcinoma patients with anaplastic lymphoma kinase (ALK) rearrangement, epidermal growth factor receptor (EGFR) mutation and both negative were included in the present study. The incidence of VTE of these patients was calculated. We then randomly selected ALK-rearrangement-positive and -negative lung adenocarcinoma tissues (n=29 and n=26, respectively) and detected TF protein expression via immunohistochemistry. RESULTS: At a median follow up of 2.5 years, 5.85% (n=30/513) patients with advanced lung adenocarcinoma experienced VTE. Compared to patients with EGFR mutation (n=11/218, 5.05%) or both negative (n=13/266, 4.89%), patients with ALK-rearrangement were more likely to develop VTE (n=6/29, 20.69%; P=0.006, P=0.004; respectively). In ALK-rearrangement-positive tissues, 41.67% (n=10/24) had a high TF protein expression; the incidence was significantly higher than the TF protein expression in ALK-negative tissues (11.54%, n=3/26, P=0.015). CONCLUSIONS: ALK-rearrangement-positive NSCLC patients are more likely to develop VTE; this might be due to a higher TF expression in tumor tissues.