thymosin and Gastrointestinal-Stromal-Tumors

Thymosin beta-4 (Tβ4) is a protein that is linked to a number of important biological actions and recently tumor progression and poor prognosis of some tumors. The aim of this study was to evaluate Tβ4 expression in gastric GISTs and correlate with some clinicopathological characteristics related with prognosis and clinical outcome in order to add further data to the current literature.. Tβ4 antibody was applied to the 4μm-thick paraffin sections of 57 gastric GISTs by immunohistochemistry.. Tβ4 expression was found to be directly corrrelated with higher risk groups, tumor size, mitotic count, cellularity, and necrosis while it was inversely correlated with overall survival (OS) by univariate analysis (p=0.000, p=0.001, p=0.000, p=0.025, p=0.023, and p=0.042, respectively). The direct association between Tβ4 expression and risk groups were also supported by multivariate analysis (p=0.000, β=0.497, t=4.374).. Overexpression of Tβ4 was found to be related with predictive characteristics for tumor progression and adverse prognosis. Thus, we suggest that overexpression of Tβ4 might play a role in the progression of gastric GISTs and might be used as a potential prognostic tool as well as a target for novel therapies.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease Progression; Female; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Prognosis; Retrospective Studies; Risk Factors; Thymosin; Young Adult

Thymosin beta-4 (Tβ(4)) is a major actin-sequestering molecule that contributes to cell growth, differentiation, motility, survival, mitosis and angiogenesis. It is overexpressed in certain type of carcinoma and fibrosarcoma cell lines and is associated with metastatic potential. The aim of this study was to investigate the relationship between Tβ(4) expression and clinicopathologic features and VEGF status in gastrointestinal stromal tumors (GISTs). Retrospectively, 60 GISTs were re-examined and immunohistochemistry for Tβ(4) and VEGF was performed. Increased expression of Tβ(4) and VEGF was observed in 26 (43.3%) and in 19 (31.6%) of the tumors, respectively. Tβ(4) expression was positively correlated with VEGF expression (p < 0.01). Tβ(4) and VEGF expression were significantly associated with tumor size (p = 0.00 and p = 0.02, respectively) and high mitosis (p = 0.03 and p = 0.00, respectively). Although Tβ(4) expression was positively associated with pleomorphism (p = 0.01), VEGF expression was positively associated with necrosis (p = 0.03). Tβ(4) expression was related with local recurrence and/or metastasis (p = 0.03), but VEGF expression was not (p = 0.12). We firstly demonstrate the presence of Tβ(4) protein in GISTs. Our study reveals that increased expression of Tβ(4) could be considered as an indicator of aggressive behavior of tumor.

Topics: Adult; Aged; Aged, 80 and over; Biomarkers, Tumor; Disease-Free Survival; Female; Gastrointestinal Neoplasms; Gastrointestinal Stromal Tumors; Humans; Immunohistochemistry; Kaplan-Meier Estimate; Male; Middle Aged; Retrospective Studies; Thymosin; Vascular Endothelial Growth Factor A