Phospho-Stat3 expression and correlation with VEGF, p53, and Bcl-2 in gastric carcinoma using tissue microarray

Abstract

The signal transducer and activator of the transcription (Stat)-family of proteins are latent cytoplasmic transcription factors that transmit signals from cytokines and growth-factor receptors to the nucleus. Stat proteins, especially Stat3 and Stat5, are constitutively activated in various solid tumors and hematological malignancies. However, the role of Stat3 signaling in gastric carcinoma has not yet been fully determined. This study was conducted to investigate the clinical value of phospho-Stat3 expression in gastric carcinoma. Expression of phospho-Stat3 (Tyr705), vascular endothelial growth factor (VEGF), p53, and Bcl-2 was determined by immunohistochemical staining of tissue microarrays from 137 cases of resected gastric cancer specimens. We evaluated the relationships among phospho-Stat3, VEGF, p53, and Bcl-2 expression and the correlation between expression of these proteins and various clinicopathological factors, including overall survival. Phospho-Stat3 nuclear expression was observed in 18.2% of the cases. Of the total number of cases, 68.6% were positive for VEGF, 40.1% for p53, and 11.7% for Bcl-2. Phospho-Stat3 expression correlated with VEGF (p=0.021) and Bcl-2 (p=0.005) expression. Positive phospho-Stat3 staining was significantly associated with poor pathological grade. However, there was no significant difference in other clinicopathological parameters, such as tumor stage (T, N, M), pathological type, relapse-free survival, and overall survival between the phospho-Stat3-positive and -negative groups. Co-expression of phospho-Stat3 and VEGF was found in many patients with N3 and Stage IV disease. These results suggest that phospho-Stat3 expression might be associated with angiogenesis, anti-apoptosis, and tumor progression. Further studies are needed to determine the role of phospho-Stat3 in gastric cancer.