ObjectiveTo investigate the expression of tumor metastasis associated genes-1 (MTA1) and vascular endothelial growth factor-C (VEGF-C) in esophageal squamous cell carcinoma (ESCC) and the relationship between them and lymphangiogenesis. MethodA total of 107 patients who received excision for ESCC in the Cardiothoracic Surgery Department of Suining Central Hospital from March 2013 through January 2014 were enrolled. And the paraffinembedded esophageal tissues in 56 healthy persons were collected. The expression of MTA1 and VEGF-C in ESCC was detected using the immunohistochemical method. And D2-40 was used to label the micro-lymphatic endothelial cells of the tumor tissues while the micro-lymphatic vessel density (LVD) was counted. Meanwhile, a statistical analysis was performed for the relationship between MTA1 with VEGF-C and clinical pathological parameters. ResultsThe expression rates of MTA1 protein and VEGF-C protein in ESCC (50.4% and 58.8%, respectively) were higher than those in normal esophageal tissues with a statistical difference (P<0.05). Besides, their high expression rates in stage T3/T4 ESCC and lymph node metastasis group were significantly higher than those in stage T1/T2 ESCC and metastasisfree group, with statistical differences (P<0.05). The high expression rates of MTA1 and VEGF-C protein in ESCC with different TNM stages were compared using Kruskal-Wallis test with statistical differences (P<0.05). Moreover, a positive correlation existed in the expression level between MTA1 protein and VEGF-C protein of ESCC (Spearman coefficient r=0.512, P=0.000). And LVD of the high expression group for MTA1 protein and VEGF-C protein was statistically different from that of the low expression group (P<0.05). ConclusionThe expression of MTA1 is positively correlated with the expression of VEGF-C in ESCC. And they may co-promote lymphangiogenesis and lymphatic metastasis in ESCC. Therefore, both can be used as the laboratory indicators to determine the prognosis of ESCC.
【Abstract】Objective To introduce the current studies of the role of vascular endothelial growth factorC (VEGFC) and VEGFD in lymphangiogenesis and lymph node metastasis of gastrointestinal neoplasma. Methods The related literatures in recent 5 years were reviewed. Results The growth factors VEGFC and VEGFD enhance lymphangiogenic metastasis of gastrointestinal neoplasma with the property of angiogenesis and lymphangiogenesis. In gastric adenocarcinoma, VEGFC mRNA and tissue protein expression correlate with lymphatic invasion, lymph node metastasis, venous invasion and reduced 5year survival rates. The role of VEGFC in esophageal squamous cancer and colorectal cancer and VEGFD in colorectal cancer is not certain, with conflicting reports in the published literatures.Conclusion The VEGFC, VEGFD/VEGFR3 signal pathway may become the ideal target for inhibition of tumor proliferation and metastases, antilymphangiogenesis therapy may be a novel potential strategy in tumor biological therapy.
Abstract: Objective To evaluate the significance of expression of vascular endothelial growth factor-C （VEGF-C） and cytokeratin 19 （CK19） in patients with stage I non-small cell lung cancer （NSCLC）. Methods A total of 269 patients with NSCLC who underwent standard lobectomy and lymph node dissection by the same surgical team in our hospital from January 2004 to June 2005 were included in this study. All the clinical data and follow-up results were complete, and all the pathological specimens were well kept. No preoperative or postoperative adjuvant therapy such as radiotherapy and chemotherapy was administered to those patients. Expressions of VEGF-C in cancer tissues was detected by immunohistochemical streptavidin-peroxidase （S-P） method, and CK19 was marked to examine micrometastasis in hilar and mediastinal lymph nodes. Clinical outcomes, pathological results and follow-up data were analyzed in combination with VEGF-C and CK19 expression. Results VEGF-C expression was not statistically different between different category in sex（Hc=1.722，P=0.084）, age （Hc=0.914，P=0.360）, smoking （Hc=2.440，P=0.295）, pathology type （Hc=5.668，P=0.058）or tumor size （Hc=0.165，P=0.920） . VEGF-C expression was statistically different between different groups of pathological differentiation （Hc=29.178，P=0.000). CK19 expression was not statistically different between different category in sex（χ2=0.000，P=0.999）, age （χ2=0.005，P=0.999）, smoking （χ2=2.294，P=0.317）, pathology type （χ2=0.573，P=0.289）, tumor size（χ2=0.006，P=0.999）, and pathological differentiation （χ2=2.927，P=0.231）. Five-year survival rate was statistically different between different grade of VEGF-C expression （χ2=37.318，P=0.000), and was also statistically different between positive group and negative group of CK19 （χ2=39.987，P=0.000). There was statistical difference between different grade of VEGF-C expression and positive rate of CK19 （χ2=25.954，P=0.000). Conclusion Expression of VEGF-C and CK19 is closely related to postoperative 5-year survival of patients with stage I NSCLC. Detection of VEGF-C and CK19 is of great clinical significance as it is helpful to predict patient prognosis and choose proper postoperative adjuvant therapy.
Objective To investigate the expressions of vascular endothelial growth factor-C (VEGF-C) and its receptor Flt-4 in hepatocellular carcinoma (HCC), in order to analyze the relationships among their expressions, angiogenesis, lymph-genesis, and clinicopathologic features of HCC. Methods Sixty-two cases of HCC and 15 cases of normal hepatic tissue were studied with immunohistochemical method in order to inspect the expressions of VEGF-C and Flt-4, and to calculate the microvessel density (MVD) marked by CD34 and the lymphatic vessel density (LVD) marked by Flt-4. Besides their correlations, their relations with clinicopathologic features of HCC were further analyzed. Results The positive rates of VEGF-C and Flt-4 were obviously higher in HCC than those in normal hepatic tissue (Plt;0.05, Plt;0.01). The expression of VEGF-C in HCC was remarkably related with portal vein tumor emboli, histological differentiation of HCC, and postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). The expression of Flt-4 in HCC was also related with histological differentiation and postoperative recurrence (Plt;0.05, Plt;0.01). MVD was related with tumor size, TNM clinical stage, histological differentiation, portal vein tumor emboli, and postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). LVD was related with histological differentiation, postoperative recurrence and metastasis (Plt;0.05, Plt;0.01). Additionally, there was positive correlation between VEGF-C and Flt-4, MVD or LVD, Flt-4 and MVD or LVD, MVD and LVD, respectively (Plt;0.01). Conclusions VEGF-C and Flt-4 are highly expressed in HCC, and are related with postoperative recurrence, are positive correlated with MVD and LVD. It suggests that VEGF-C/Flt-4 might has an effect on progression and prognosis of HCC through promoting angiogenesis and lymph-genesis.
Objective To study the expressions and clinical significance of matrix metalloproteinases-2 (MMP-2) and vascular endothelial growth factor-C (VEGF-C) in patients with papillary thyroid carcinoma (PTC). Methods SP immunohistochemical technique was used to detect the expressions of MMP-2 and VEGF-C in 78 cases of PTC and 18 cases of thyroid benign tumors.Results The positive expression rates of MMP-2 and VEGF-C in PTC （80.77%, 75.64%） were significantly higher than those of the thyroid benign tumor （11.11%, 22.22%）, P＜0.05. The expressions of MMP-2 and VEGF-C were correlated to the degree of infiltration and lymph node metastasis in PTC: In those which infiltrated to or over the thyroid capsular, or had clinical neck lymph node metastasis, the positive expression rates were significantly higher than those in the other cases which had confined invasion of thyroid capsular or non-clinical metastasis of neck lymph node (P＜0.05). And during the follow-up of 41 patients who didn’t have clinical neck lymph node metastasis before operation, the positive expression rates of those who had clinical neck lymph node metastasis were significantly higher than those in the other patients who didn’t have neck lymph node metastasis (P＜0.05). There was significantly positive correlation between the expressions of MMP-2 and VEGF-C in PTC （Gamma=0.846， P＜0.05）. Conclusions MMP-2 and VEGF-C may be used to distinguish malignant and benign thyroid tumor; The expressions of MMP-2 and VEGF-C are correlated with the degree of infiltration and neck lymph node metastasis in PTC; Combined detection of MMP-2 and VEGF-C will be more accurate to predict condition of lymph node metastasis.
Objective To explore the effect of vascular endothelial growth factor-C (VEGF-C) gene transfection on the expression level of VEGF-C in human breast cancer MCF-7 cell. Methods The constructed VEGF-C gene eukaryotic expression vector was transfected into the human breast cancer MCF-7 cell by using lipofectamine transfection reagents， and the positive cell clones were obtained through G418 selection after transfection. The expressions of VEGF-C mRNA and protein were detected by RT-PCR and Western blot respectively. Results Following the transfection of the VEGF-C recombination plasmid, there were significant differences on the expression levels of VEGF-C mRNA and protein between pcDNA3.1-VEGF-C transfection group and pcDNA3.1 transfection group （12.382±2.183 vs 6.039±1.950, P＜0.01; 0.971±0.186 vs 0.594±0.196, P＜0.05). Conclusion With the transfection of pcDNA3.1-VEGF-C vector by using the liposome, the expression levels of VEGF-C mRNA and protein rise up in breast cancer MCF-7 cell.
【Abstract】 Objective To research the significance on expression of vascular endothelial growth factor-C (VEGF-C) in human breast carcinoma, benign diseases and normal mammary gland by self-constructed tissue chips and research its relationship to regional lymph node metastasis. Methods The tissue chips containing specimens of breast carcinoma, breast benign disease and normal mammary gland were designed and constructed. The expression of VEGF-C in the specimens was detected by the tissue chips and immunohistochemical method, and researched the relationship of the expression of VEGF-C in breast cancer with regional lymph node metastasis. Results The positive rates of VEGF-C in the centre and borderline of carcinoma and distant mammary gland （the distance from the tumor’s bouncary ＞3 cm） were 69.4%（68 /98）, 69.1%（67 /97） and 52.9%（36 /68）, respectively， but not in benign disease and normal mammary gland specimens. The positive rates of VEGF-C in the centre and borderline of carcinoma in lymph node metastasis group 〔75.0%（51/68）， 76.1%(51/67)〕 were significantly higher than that of no metastasis group 〔25.0%（17/68），23.9%(16/67)〕, P＜0.05. The positive rates of VEGF-C in the centre and borderline of carcinoma and distant mammary gland were no correlation with size, type and clinical stage of tumor. Conclusion The tissue chips is high efficiency and well quality control in multiple factor investigation. There are overexpression of VEGF-C in primary breast cancer, and that may play an important role in lymph node metastasis.