Phosphorylated Smad2 in Advanced Stage Gastric Carcinoma

Immunohistochemical staining with anti-p-Smad2 was performed on paraffin-embedded specimens from 135 patients with advanced gastric adenocarcinomas. We also evaluated the relationship between the expression levels of p-Smad2 and clinicopathologic characteristics of patients with gastric adenocarcinomas.The p-Smad2 expression level was high in 63 (47%) of 135 gastric carcinomas. The p-Smad2 expression level was significantly higher in diffuse type carcinoma (p = 0.007), tumours with peritoneal metastasis (p = 0.017), and tumours with lymph node metastasis (p = 0.047). The prognosis for p-Smad2-high patients was significantly (p = 0.035, log-rank) poorer than that of p-Smad2-low patients, while a multivariate analysis revealed that p-Smad2 expression was not an independence prognostic factor.The expression of p-Smad2 is associated with malignant phenotype and poor prognosis in patients with advanced gastric carcinoma.Transforming growth factor β (TGFβ) is a multifunctional cytokine and one of most important pathways for cancer cells [1,2]. TGFβ binds to two different serine/threonine kinase receptors (TβR), termed type I and type II. The activated TβR type I kinase phosphorylates Smad2 and Smad3. Phosphorylated Smad2 (p-Smad2) and p-Smad3 are oligomerized with Smad4, migrate into nucleus and regulate transcription [1,3]. In normal epithelial cells, TGFβ is a potent inhibitor of proliferation, and it has been considered a tumour suppressor. Although TGFβ acts as a tumour suppressor in early-stage tumours, during tumour progression the TGFβ antiproliferative function is lost, and in certain cases TGFβ becomes an oncogenic factor inducing cell proliferation, invasion, angiogenesis, and immune suppression [4,5]. It has been reported that TGFβ can signal not only through Smad-dependent, but also Smad-independent pathways [6]. Because of the dual aspects of TGFβ in oncogenesis, Smad signal might be a critical integrator of TGFβ receptor signaling transduction systems, altho