Abstract
AimsTransforming growth factor-β (TGF-β), fascin, nuclear factor-kappa B (NF-κB) p105, protein-kinase C-zeta (PKC-ζ), partioning-defective protein-6 (Par-6), E-cadherin and vimentin are tumor promoting molecules through mechanisms involved in cell dedifferentiation. In soft tissue sarcomas, their expression profile is poorly defined and their significance is uncertain. We aimed to investigate the prognostic impact of TGF-β1, NF-κB p105, PKC-ζ, Par-6α, E-cadherin and vimentin in non-gastrointestinal stromal tumor soft tissue sarcomas (non-GIST STSs).Patients and MethodsTumor samples and clinical data from 249 patients with non-GIST STS were obtained, and tissue microarrays (TMAs) were constructed for each specimen. Immunohistochemistry (IHC) was used to evaluate marker expression in tumor cells.ResultsIn univariate analysis, the expression levels of TGF-β1 (P = 0.016), fascin (P = 0.006), NF-κB p105 (P = 0.022) and PKC-ζ, (P = 0.042) were significant indicators for disease specific survival (DSS). In the multivariate analysis, high TGF-β1 expression was an independent negative prognostic factor for DSS (HR = 1.6, 95% CI = 1.1–2.4, P = 0.019) in addition to tumor depth, malignancy grade, metastasis at diagnosis, surgery and positive resection margins.ConclusionExpression of TGF-β1 was significantly associated with aggressive behavior and shorter DSS in non-GIST STSs.
Highlights
Soft tissue sarcomas (STS) are malignant tumors arising from extraskeletal connective tissues
Expression of transforming growth factor beta 1 (TGF-b1) was significantly associated with aggressive behavior and shorter Disease-specific survival (DSS) in non-GIST STSs
We investigate the expression of a panel of seven molecular biomarkers in 249 non-GIST STS patients
Summary
Soft tissue sarcomas (STS) are malignant tumors arising from extraskeletal connective tissues. They are group of heterogeneous neoplasms, consisting of more than 50 subtypes, but comprise less than 1% of adult malignancies [1,2]. The prognostic factors determining tumor progression and patients’ fate include tumor grade, size, location, depth, histological entity, positive resection margins and presence of local recurrence [4,5,6,7,8,9,10]. Malignant transformation in epithelial tumors is described as epithelial-to-mesenchymal transition (EMT). EMT is defined as a sequence of protein modifications and transcriptional events in response to a certain set of extracellular stimuli leading to a stable, but sometimes reversible, cellular change [14]
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