Granzyme B在原发及淋巴转移性胃癌细胞中的差异表达及其与肿瘤血管生成的关系

Differential expression of Granzyme B in tumor cells between primary and metastatic gastric cancer and its potential role in tumor angiogenesis

AIM: To investigate the potential role of Granzyme B (GrB) in the biological behavior of gastric cancer, such as angiogenesis and lymphatic metastasis. METHODS: The identification of GrB expression in gastric cancer cells was performed immuno-histologically in patients with primary gastric cancers (PGC, n = 35) and lymphoid metastatic gastric cancer (LMGC, n = 23), and GrB+ cyto-toxic T lymphocytes (CTL) served as positive internal control.The antibodies recognizing vascular endothelial growth factor (VEGF) and CD34 were employed to detect the VEGF expression and microvascular density (MVD), respectively. RESULTS: The positive rate of GrB expression was relatively lower in PGC with lymphoid metastasis than that without metastasis, but no significant difference was observed (P = 0.709). The positive rate of GrB expression in LMGC was significantly higher than that in the corresponding PGC (P = 0.038). The synchronous expression rate of GrB and VEGF came up to 57.1%, while there was no significant correlation between them. A significant negative correlation was found between the level of GrB expression and MVD (r = -0.421, P = 0.012) in PGC. VEGF expression was showed to have no significant effect on MVD in GrB positive PGC (P = 0.494). However, the decreased MVD in VEGF+ PGC was remarkably associated with GrB expression (P = 0.023), and similar feature was exhibited in VEGF negative PGC (P = 0.134). The lowest and the highest MVD were demonstrated in PGC with positive GrB and negative VEGF, and PGC with positive VEGF and negative GrB, respectively (P = 0.013). CONCLUSION: The over-expression of GrB in gastric cancer cells might contribute to the inhibition of tumor angiogenesis, but also might contribute to the survival potential of diffused tumor cells in lymph gland.