Survivin mRNA expression and its relationship with VEGF and clinicopathologic parameters in breast cancer.
Authors: J Tang, J Zhang, J Wu, J Zhao
Journal: Cancer Research (2009)

Abstract Abstract #4045 Background: Survivin, a novel member of apoptosis (IAP) gene family, is one of the most cancer-specific proteins identified to date. It has multiple functions including cytoprotection, inhibition of cell death, and cell-cycle regulation, especially at the mitotic process stage, all of which favor cancer survival. Recently the anti-apoptosis effect of survivin is also manifested in endothelial cells potentially enhancing angiogenesis, while tumor angiogenesis has been known to be related to invasiveness, metastasis and prognosis of breast cancer. This study aimed to establish a real-time fluorescence RT-PCR method with modified quantitative mode to accurately determine the expression levels of survivin mRNA, and to explore survivin relationship with vascular endothelial growth factor (VEGF) and their biological roles in the development and progression of breast cancer.&amp;#x2028; Materials and Methods: Based on the established method which used“external calibration curve + internal control gene” as quantitative mode, the levels of survivin mRNA expression were determined in 39 breast cancer tissues, their para-tumor tissues and 22 breast benign tumor tissues, respectively. VEGF protein expression by an immunohistochemical SP method was also analyzed. SPSS 13.0 statistical software was used to analysis the relationship between these two factors and their associations with clinical pathological parameters.&amp;#x2028; Results: This developed system could detect survivin mRNA level down to 150 copies/µg total RNA. The mean level of surviving mRNA in breast cancer tissues (397,788 ± 50,710 copies /µg total RNA) was significantly higher than that in control tissues (adjacent tissues and benign tumor tissues, 73,095 ± 8,599; P = 0.004). In the cancer specimens, 87.2% (34/39) were positive for Survivin mRNA expression, and 82.1% (32/39) were positive for VEGF protein expression, which showed significant differences comparing with the control tissues (50% and 11.9%; P&amp;lt;0.05). Survivin mRNA levels were not correlated to the cancer patients' age, menopausal status and pathological types (P&amp;gt;0.05), but related to large tumor size, high invasion grade and the presence of lymph node metastasis (P&amp;lt;0.05). Same was for VEGF except for a marginally significant relationship with metastasis status (r=0.312, P=0.053). Correlation analysis indicated a positive correlation between survivin mRNA level and VEGF protein expression in the breast cancer, r=0.724, P&amp;lt;0.0001.&amp;#x2028; Conclusion: The real-time fluorescence RT-PCR assay with new quantitative mode for survivin expression may provide more reliable and intuitionistic data with good sensitivity and specificity. In breast cancer tissues, Survivin and VEGF are over-expressed and correlated each other. They play an important role in breast cancer development and progression in coordinated way, and may be the promising molecular targets for new anti-cancer therapies. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 4045.