Src activity is increased in gastrointestinal stromal tumors--analysis of associations with clinical and other molecular tumor characteristics.

ABSTRACT

BACKGROUND: Increased activity of Src has been found in several human cancers, and often is associated with poor clinical outcome. The present study aimed to determine whether Src activity is increased in gastrointestinal stromal tumors (GIST), and whether it correlates with established tumor or patient characteristics and prognosis. METHODS: Tumor/normal tissues of 29 patients were analyzed for Src activity/protein with kinase assays, and for VEGF/VEGFR with immunohistochemical staining. RESULTS: Src activity was higher in tumor than in normal tissues (P = 0.093). However, when imatinib responders were excluded from the analyses, it was significantly higher in the tumor tissue (P = 0.017). Additionally, it was higher in primary compared to recurrent tumors or metastasis (P = 0.04). Univariate survival analysis showed a longer overall survival for patients with high Src activity (P = 0.038). In multivariate analysis, the response to imatinib treatment was the only survival-influencing factor (P = 0.072). CONCLUSIONS: Src activity is increased in GIST. In contrast to most other tumor entities, it does not correlate with poor clinical outcome, but decreases during the progression from primary tumor to recurrence and metastasis, especially under therapy with imatinib. Additionally, our results show that higher Src activity is associated with longer overall survival.