BACKGROUND/AIMS: Phosphatase and tensin homolog deleted on chromosome ten (PTEN) is a recently clarified tumor suppressor gene located in 10q23.3. Alterations of this gene are associated with tumor progression and unfavorable outcome in various human cancers. Recently, PTEN has a possible role in angiogenesis by modulating angiogenic factor including vascular endothelial growth factor (VEGF). The aim of this study was to investigate the roles of PTEN and VEGF status for angiogenesis in human gastric cancer. METHODS: We conducted an immunohistochemical investigation of PTEN and VEGF expression in 90 cases of paraffin section obtained from gastric cancer patients undergone surgical treatment. RESULTS: Negative expression of PTEN and positive expression of VEGF in gastric cancer tissues, were demonstrated in 40.0% and 77.8% of cases, respectively. However, no significant correlation was found between PTEN, VEGF expression and various clinicopathological parameters. PTEN expression did not correlate significantly with VEGF expression (p=0.301). High microvessel density (MVD) was significantly associated with lymph node metastasis and poor survival (p=0.014, 0.011, respectively). The mean MVD value of PTEN negative tumors was 90.4+/-43.0 and significantly higher than that of PTEN positive tumors (p=0.028). The mean MVD value of VEGF positive tumors was 86.4+/-36.7 and significantly higher than that of VEGF negative tumors (p=0.002). The mean MVD value of PTEN negative and VEGF positive tumors was 98.0+/-42.2, and significantly higher than those of the others. CONCLUSIONS: These results suggest that loss of PTEN expression may play a critical role in tumor progression and metastasis by stimulating tumor angiogenesis in human gastric cancer.
Adult ; Aged ; Carcinoma/*blood supply/metabolism/mortality/secondary ; Disease Progression ; Female ; Humans ; Immunohistochemistry ; Male ; Microcirculation/pathology ; Middle Aged ; Neovascularization, Pathologic/*metabolism ; PTEN Phosphohydrolase/*metabolism ; Stomach Neoplasms/*blood supply/metabolism/mortality ; Survival Rate ; Vascular Endothelial Growth Factor A/metabolism

Adenocarcinoma ; blood supply ; metabolism ; mortality ; secondary ; Adult ; Aged ; Female ; Humans ; Lymphatic Metastasis ; Male ; Microcirculation ; Middle Aged ; Neovascularization, Pathologic ; metabolism ; pathology ; Prognosis ; RNA, Messenger ; biosynthesis ; genetics ; Receptors, Cell Surface ; biosynthesis ; genetics ; Receptors, Urokinase Plasminogen Activator ; Stomach Neoplasms ; blood supply ; metabolism ; mortality ; pathology ; Survival Rate ; Vascular Endothelial Growth Factor A ; metabolism

Thymidine phosphorylase (TP) has shown to be up-regulated in several cancers and to play a role in angiogenesis and invasion. Most studies regarding TP have focused on cancer cells. Recently, evidences suggest that TP in cancer-infiltrating inflammatory cells (CIICs) also affect the cancer cell behavior. To evaluate the significance of TP expression of CIICs in gastric cancer, we assessed TP expression of cancer cells and CIICs separately using immunohistochemical assay on 116 paraffin-embedded tissue samples from stomach cancer patients and investigated their clinical significance. When subjects were divided into 4 groups according to the TP expression: cancer/matrix (+/+), C/M (+/-), C/M (-/+), and C/M (-/-), intratumoral microvessel density scores were higher in the C/M (+/-) group than in the C/M (-/-) group (p=0.02). For lymph node metastasis and survival, there were no significant differences among the 4 groups. However, there were significant differences in survival (p=0.035) and LN metastasis (p=0.023) between the two groups divided by TP expression of CIICs alone irrespective of TP expression of cancer cells. Taken together, this study suggested the TP expression in CIICs could affect lymph node metastasis and patients' survival in gastric cancer.
Adult ; Aged ; Female ; Humans ; Immunohistochemistry ; Inflammation/*enzymology/pathology ; Kaplan-Meiers Estimate ; Lymphatic Metastasis ; Lymphocytes, Tumor-Infiltrating/*enzymology/pathology ; Male ; Microcirculation/pathology ; Middle Aged ; Neovascularization, Pathologic ; Prognosis ; Stomach Neoplasms/blood supply/*enzymology/mortality/pathology ; Thymidine Phosphorylase/*metabolism