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Src activity is increased in gastrointestinal stromal tumors—Analysis of associations with clinical and other molecular tumor characteristics
Author(s) -
Rotert Julia Valerie,
Leupold Jörg,
Hohenberger Peter,
Nowak Kai,
Allgayer Heike
Publication year - 2014
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.23544
Subject(s) - medicine , gist , stromal tumor , imatinib , proto oncogene tyrosine protein kinase src , immunohistochemistry , metastasis , stromal cell , oncology , univariate analysis , imatinib mesylate , primary tumor , tumor progression , pathology , multivariate analysis , cancer , receptor , myeloid leukemia
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. J. Surg. Oncol. 2014 109:597–605 . © 2014 Wiley Periodicals, Inc.