Growth, invasion, metastasis, differentiation, angiogenesis and apoptosis of gastric cancer regulated by expression of PTEN encoding products.

Aim: To investigate expression of PTEN in gastric cancer and to explore its roles in tumorigenesis and progression of gastric cancer.

Methods: Formalin-fixed and paraffin-embedded tissues of adjacent non-tumor mucosa and primary foci from 113 cases of gastric cancers were studied for the expression of PTEN and Caspase-3 and microvessel density (MVD) by streptavidin-peroxidase (S-P) immunohistochemistry with antibodies against PTEN, Caspase-3, and CD34. The relationship between PTEN and Caspase 3 expression and clinicopathological parameters of tumors was compared.

Results: Primary gastric cancer cells expressed PTEN less frequently than adjacent epithelial cells of primary foci (54.9 % vs 89.4 %; P=0.000, chi(2)=33.474). PTEN expression was significantly associated with invasive depth (P=0.003, rs=0.274), metastasis (P=0.036, rs=0.197), growth pattern (P=0.008, rs=0.282), Lauren's classification (P=0.000, rs=0.345), and histological classification (P=0.005, rs=0.262) of tumors, but not with tumor size (P=0.639, rs=0.045), Borrmann's classification (P=0.544, rs=0.070) or TNM staging (P=0.172, rs=0.129). PTEN expression was negatively correlated with MDV in primary gastric cancer (P=0.020, F=5.558). Primary gastric cancer cells showed less frequent immunoreactivity to Caspase-3 than adjacent epithelial cells of primary foci (32.7 % vs 50.4 %; P=0.007, chi(2)=7.286). Caspase-3 expression was dependent of PTEN expression in primary gastric cancer cells (P=0.000, chi(2)=15.266).

Conclusion: Down-regulated expression of PTEN plays an important role in tumorigenesis, progression, growth, differentiation and angiogenesis of gastric cancer. Low expression of PTEN can decrease expression of Caspase-3 to disorder apoptosis of tumor cells, which might explain the molecular mechanisms of PTEN contributions to tumorigenesis and progression of gastric cancer.