The Study Of Lymphangiogenesis And Lymphatic Vessel Density In Colorectal Cancer

Objective In order to study mechanism of lymphangiogenesis,the expression of vascular endothelial growth factor C(VEGF-C),vascular endothelial growth factor receptor 3(VEGFR-3),and hypoxia inducible factor-1α(HIF-1α) in colorectal carcinoma(CRC) were researched,simultaneously lymphatic vessel density(LVD) of CRC was counted.The relationship between these data and clinicopathologic features of CRC was demonstrated to support theoretical basis and experimental evidence for novel diagnosis and treatment of CRC.Methods The level of mRNA transcription and protein expression of VEGF-C, VEGFR-3 and HIF-1αin both tumor specimens and surgical marginal tissue of 60 cases with CRC were determined by real-time quantitative PCR using fluorescence and immunohistochemistry staining,as well as lymph vessel density was counted using anti-podoplanin monoclonal antibody.ResultsLVD of tumor tissue(17.72±6.93) was significant higer than that of surgical margin (8.90±2.40),P＜0.05.In tumor speciment,there were a statistical difference in defferent tumor differentiation,invasive depth,and lymph node metastasis and Dukes stages(P＜0.05),While,the different counts were not detected in different age,gender and histological types(P＞0.05).In 60 cases with CRC,the expression of VEGF-C mRNA was 0.81±0.33,and 39 cases were positive in anti-VEGF-C immunohistochemistry staining.These were respective significant decreasing in specimens of surgical margin(0.62±0.28,15 positive cases),P＜0.05.In tumor speciment,there were a statistical difference in defferent tumor differentiation,invasive depth,and lymph node metastasis and Dukes stages(P＜0.05).There was no difference detected in different age,gender and histological types(P＞0.05).In 60 cases with CRC,the expression of VEGFR-3 mRNA was 0.71±0.29,and 47 cases were postive in anti-VEGFR-3 immunohistochemistry staining.These were respective significant decreasing in specimens of surgical margin(0.49±0.17,16 positive cases),P＜0.05.In tumor speciment,there were a statistical difference in defferent tumor differentiation,invasive depth,and lymph node metastasis and Dukes stages(P＜0.05).It was not showing the different expression of VEGFR-3 in different age,gender and histological types(P＞0.05).In 60 cases with CRC,the expression of HIF-1αmRNA was 0.79±0.31,and 40 cases were postive in anti-HIF-1αimmunohistochemistry staining.These were respective significant decreasing in specimens of surgical margin(0.52±0.17,16 positive cases), P＜0.05.In tumor speciment,there were a statistical difference in defferent tumor differentiation,invasive depth,and lymph node metastasis and Dukes stages(P＜0.05). The different counts were not detected in different age,gender and histological types (P＞0.05).There were some positive correlationships were detected in this study,such as the molecular expression of tumor speciments in HIF-1αwith VEGF-C,VEGF-C with VEGFR-3,as well as VEGF-C and VEGFR-3 with LVD.Conclusion It is demonstration that LVD was relationship with CRC invasion and metastasis because LVD counts was difference in different groups of tumor differentiation,infiltration depth,and lymph node metastasis and Dukes stages.The study also shows the correlation between expression of VEGF-C,VEGFR-3,HIF-1αwith tumor differentiation,invasive depth,and lymph node metastasis and Dukes stages.The positive relationship of VEGF-C and VEGFR-3 with LVD,HIF-1αwith VEGF-C,VEGF-C with VEGFR-3 suggestion that VEGF-C is the key regulator in lymphatic vessel formation and HIF-1αmay be a regularmolecular in upstream.