Expressão de VEGF-C, VEGF-D, mensuração da densidade linfática e da proliferação endotelial linfática em neoplasias de glândulas salivar / Expression of VEGF-C, VEGF-D density measurement of lymphatic and lymphatic endothelial proliferation in salivary gland neoplasms

As neoplasias de glândulas salivares exibem uma grande diversidade morfológica e comportamentos biológicos variados o que suscita o interesse na pesquisa destas lesões. A disseminação das células tumorais é um passo inicial para a progressão de neoplasias malignas e, dentro deste contexto, os vasos linfáticos neoformados são considerados essenciais para que ocorra essa disseminação. O papel do VEGF (fator de crescimento endotelial vascular) na formação dos vasos é fato conhecido mas, pouco se sabe a respeito de sua participação em tumores de glândula salivar. Desta forma, o objetivo deste estudo foi avaliar a expressão do VEGF-C e VEGF-D, a densidade linfática tumoral (D2-40) e a proliferação endotelial linfática (dupla marcação D2-40/Ki-67) em uma série de neoplasias de glândulas salivares. A amostra foi composta por 20 adenomas pleomórficos, 20 carcinomas adenóides císticos, 20 carcinomas mucoepidermóides e 10 casos de tecido glandular salivar com características de normalidade para efeito comparativo. Todos os casos estudados exibiram expressão positiva para VEGF-C em região peritumoral e intratumoral, não sendo encontrada diferenças de imunoexpressão entre os grupos. No entanto, o grupo dos carcinomas adenóides císticos demonstrou diferença significativa da imunoexpressão do VEGF-C segundo o padrão cribriforme e sólido (p = 0,004). A maioria dos casos constantes do presente estudo, apresentou fraca marcação para VEGF-D em região peritumoral e intratumoral...

Salivary gland neoplasms exhibit a great morphological diversity and varied biological behavior which raises the interest in the study of these lesions. The spread of tumor cells is an early step in the progression of malignancies and the neoformed lymphatic vessels are considered essential in tumor dissemination. Vascular endotelial growth fator (VEGF) is a family of proteins involved in angiogenesis e lymphangiogenesis. However, in salivar tumors we have limited information on the expression. The aim of this study was to assess the expression of VEGF-C and VEGF-D, lymphatic vessel density (single-staining D2-40) and lymphatic endothelial proliferation (double labeling D2-40/Ki-67) in a series of salivary glands neoplasms. We selected 20 cases of pleomorphic adenoma, 20 of mucoepidermoide carcinoma, 20 of adenoid cystic carcinoma and 10 tissue sample of normal salivary gland. All cases studied showed positive expression of VEGF-C in intratumoral and peritumoral region, no differences in immunoreactivity was found between the groups. However, the group of adenoid cystic carcinoma showed a significant difference in immunoreactivity of VEGF-C by the cribriform and solid pattern (p = 0.004). Most of the cases included in this study showed weak immunoreactivity for VEGF-D in intratumoral and peritumoral region. In the assessment of lymphatic endotelial density peritumoral, intratumoral and total, the groups showed an increasing gradient, with lower values for the group of pleomorphic adenomas followed by mucoepidermoid carcinoma and adenoid cystic carcinoma. Lymphatic endothelial cell density was higher in malignant than benign tumors. No correlation was observed between the immunoreactivity of VEGF-C and VEGF-D in relation to tumor lymphatic density and lymphatic endothelial proliferation.

Expression of VEGF-D, D2-40, and MMP-7 and its relationship with cervical lymph node metastasis in thyroid papillary carcinoma / 中华内分泌外科杂志

Objective To detect the expression levels of vascular endothelial growth factor D ( VEGF-D) , D2-40 and MMP-7 in papillary thyroid carcinoma ( PTC) and to explore their relationship with micro lymphat-ic density, distribution,and cervical lymph node metastasis .Methods SP immunohistochemistry was used to study the expression of VEGF-D, D2-40 and MMP-7 in 38 cases of PTC with cervical lymph node metastasis , 45 cases of PTC without cervical lymph node metastasis , and 22 cases of normal thyroid tissues .Micro lymphatic density ( MLD) was counted .Results The expression level of VEGF-D in PTC with cervical lymph node metasta-sis and normal thyroid tissues had significant difference (χ2 =13.074, P=0.000, P<0.0167).The expression level of D2-40 in PTC with and without cervical lymph node metastasis had significant difference ( P<0.05 ) . MMP-7 expression in PTC with and without cervical lymph node metastasis had statistical significance ( 91.67%vs 73.33%, P<0.05).MLD in PTC with and without cervical lymph node metastasis and in normal thyroid tis-sues had statistical difference (11.7 ±3.5 vs 8.9 ±3.1 vs 3.9 ±2.7, P<0.05).Conclusion VEGF-D, D2-40 and MMP-7 are highly expressed in PTC and they are possibly related with cervical lymph node metastasis of PTC.

Study on correlation between VEGF level and malignant pleural effusion / 中国生化药物杂志

Objective Methods To explore the value of VEGF levels in serum and pleural effusion for diagnosis of benign and malignant tumors, and evaluate clinical value of VEGF-A, C, D in malignant pleural effusion.Methods Serum and pleural effusion of 34 cases patients with lung cancer were collected in our hospital, the application of ELISA method for the detection of VEGF level in serum and pleural effusion in patients with lung cancer and with benign pleural effusion.VEGF-A, C, D levels were detected.Results VEGF levels in serum and pleural effusion in malignant group were significantly higher than those in benign group(P<0.05).In addition, patients with lung cancer before initial treatment, the VEGF levels in serum and pleural effusion of distant metastasis group were significantly higher than those of without distant metastasis group(P<0.05).There was a correlation between the level of VEGF and the malignant pleural effusion(r=0.878, P<0.05).No correlation existed between VEGF level and benign pleural effusion.The content of sVEGF-A in serum had no statistical difference in cancer group and benign group.Effusion supernatants of pVEGF-A content in lung cancer group were higher than those in benign effusion group(P<0.05).pVEGF-A and sVEGF-A levels were similar in benign effusion group. Effusion supernatants pVEGF-A in malignant group was higher than that in benign effusion group(P<0.05).pVEGF-A was significantly higher than that of sVEGF-A in malignant effusion(P<0.05).Serum VEGF-C, VEGF-D content had no significant difference between cancer group and benign group. pVEGF-C, pVEGF-D content had no significant difference between cancer group and benign group.Conclusion Level of VEGF in serum and pleural effusion detection would help to diagnose and differentially diagnose benign and malignant pleural effusion.Effusion VEGF-A is different in benign and malignant effusion, which may become benign and malignant effusion tumor markers.

Radioresistance change and the mechanism of human esophaged cancer EC9706 cells in hypoxia / 中华放射医学与防护杂志

Objective To investigate the expression of hypoxia-inducible factor-1 alpha (HIF-1 α),vascular endothelial growth factor-A (VEGF-A) and vascular endothelial growth factor-D (VEGF-D)in hypoxic environment as well as the relationship between HIF-lα and VEGF-D.Methods Human esophageal cancer cell line EC9706 was cultured under hypoxia environment for 6,12 and 24 h,the cell radiosensitivity was evaluated by survival curve.HIF-1 α siRNA was constructed and transfected into human EC9706 cells.Protein expressions of HIF-1 α,VEGF-A and VEGF-D were analyzed by Western blot before and after RNA interference.Results EC9706 cells under hypoxia showed radioresistance with a SF2 of 0.62 higher than that of normoxic cells of 0.43.Moreover,the protein expressions of HIF-1α,VEGF-A and VEGF-D were all increased (F =205.24,227.88,130.55,P ＜0.05) due to hypoxia treatment.On the contrary,after HIF-1α siRNA transfer,the protein expressions of HIF-1α,VEGF-A and VEGF-D in EC9706 cells were not influenced by hypoxia treatment.Conclusions EC9706 cells in hypoxic environment was radioresistance,and the upexpressions of HIF1α,VEGF-A and VEGF-D may be involved.

Comparative Analysis of Vascular Endothelial Growth Factor-A, C, D Expression in Colorectal Cancer with Liver Metastasis

PURPOSE: We aimed to investigate the correlations between expressions of angiogenic cytokines VEGF-A, C, D of primary colorectal cancer and liver metastasis. METHODS: We examined paraffin-embedded primary colorectal cancer tissue from 45 patients who had liver resection due to colorectal liver metastasis (metastasis group) and 37 patients who had surgical resection due to colorectal cancer only (control group). In the control group, local recurrence and distant metastasis had not occurred. Immunohistochemical staining for VEGF-A, C and D was performed. We analysed the correlations between expression of VEGF-A, C and D in primary colorectal cancer tissues and clinicopathologic parameters. RESULTS: VEGF-A expressions of primary colorectal carcinoma were not different between the two groups. VEGF-C was more frequently expressed in the metastasis group (P=0.008) but VEGF-D was more expressed in the control group (P=0.003). Patients with VEGF-C negative and VEGF-D positive expression were predominant in the control group (P=0.020). Tumor location, T stage, lymph node metastasis and tumor differentiation were not related with the expressions of VEGF-A, C, D but only preoperative CEA was positively correlated with VEGF-A and C expression. CONCLUSION: Expressions of VEGF-C in primary tumor were more frequent in metastatic colorectal cancer and expressions of VEGF-D were more frequent in nonmetastatic colorectal cancer. More large-scale prospective studies for VEGF-C and D expression in colorectal cancer are necessary.

Gene Expression for Lymphangiogenic Factors in Oral Mucosal Squamous Cell Carcinoma

The Expression of Vascular Endothelial Growth Factor (VEGF)-C and VEGF-D in Early Gastric Cancer That's Invaded the Submucosa

PURPOSE: Vascular endothelial growth factor (VEGF)-C and VEGF-D are considered novel growth factors that potentially induce lymphangiogenesis and hyperplasia of lymphatic vessels. The aim of this study was to investigate whether the expressions of VEGF-C and VEGF-D are associated with the clinicophathologic factors, and particularly lymphatic invasion and lymph node metastasis, in early gastric cancers that's invaded the submucosa. METHODS: Using immunohistochemical staining, we studied the VEGF-C and VEGF-D expressions in the gastric cancer specimens from 83 patients who underwent curative gastrectomy. RESULTS: The VEGF-C and VEGF-D immunoreactivity was mainly located in the cytoplasm of the tumor cells. There was a positive VEGF-C expression in 27 of 83 cases (32.5%). The VEGF-D positivity rate was lower than the VEGF-C positivity rate. VEGF-D was positive in 20 of 83 cases (24.0%). A VEGF-C positive expression was associated with lymphatic invasion (P=0.018) and lymph node metastasis (P=0.001). However, the expression of VEGF-D had no correlation with any of the clinicopathologic factors, including lymphatic invasion and lymph node metastasis. CONCLUSION: The VEGF-C expression may have a role in lymph node metastasis of gastric cancer cells. The VEGF-C expression in tumor specimens may be a reliable marker for lymph node metastasis of early gastric cancer that's invaded the submucosa.

The Correlation between the Expression of E-cadherin, VEGF-C, VEGF-D and the Real Extent of Lymph Node Metastases using Cytokeratin 18 in Early Gastric Cancer

PURPOSE: VEGF-C and VEGF-D are angiogenetic factors, and abnormal expression of E-cadherin hasa role in the progression of gastric carcinoma. The aim of this study was to evaluate the relationship between the expression of E-cadherin, VEGF-C and VEGF-D with the presence of lymph node metastases (LNM) using cytokeratin 18 in early gastric cancer (EGC). MATERIALS AND METHODS: Immunohistochemical staining for E-cadherin, VEGF-C and VEGF-D was performed in 49 EGC patients from March 1997 to December 2002. To evaluate the real extent of LNM, 1,562 lymph nodes from 49 patients were re-examined with the use of cytokeratin 18. RESULTS: Eleven (0.7%) LNM were newly found in 12.2% (n=6) of patients. The real LNM rate was 3.6% in mucosal invasive (m) cancer and 38.1% in submucosal invasive (sm). Stage migration was seen in three patients (6.1%). Abnormal expression of E-cadherin was detected in 36.7% of the patients and expression of VEGF-C and VEGF-D was detected in 16.3% and 36.7% of the patients, respectively. Abnormal expression of E-cadherin was significantly correlated with tumor differentiation (P=0.0103) and Lauren classification (P<0.0001). There was no positive relationship of VEGF-C and VEGF-D expression with the clinicopathological findings for EGC including LNM. However, the frequency of lymph node metastases was significantly higher in patients that demonstrated abnormal expression of E-cadherin with positive immunoreactivity of VEGF-C or VEGF-D (P=0.031). CONCLUSION: In present study, we could not demonstrate a relationship between the presence of LNM and expression of VEGF-C and VEGF-D in EGC. However, VEGF-C or VEGF-D expression, in addition to the abnormal expression of E-cadherin, was correlated with the real extent of LNM in EGC.

Prediction of Invasiveness by the Expressions of CD105 (Endoglin), D2-40 and Vascular Endothelial Growth Factors A and D in the Endoscopic Biopsy Tissue of Stomach Cancer Patients

PURPOSE: CD105 (endoglin) has been shown to be a more useful marker to identify the proliferating endothelium involved in tumor angiogenesis than are the panendothelial markers. The monoclonal antibody D2-40 is a specific lymphatic endothelial marker. METHODS: We investigated CD105, lymphatic vessel marker (D2-40), vascular endothelial growth factor (VEGD)-A and the VEGF-D expressions as possible prognostic markers in the endoscopic biopsy tissue of stomach cancer patients. The pre-operative endoscopic biopsies and surgical biopsies from 73 patients were immunostained for CD105, D2-40, VEGF-A and VEGF-D. Positively stained microvessels were counted in densely vascular foci (hot spots) at a x200 field in each specimen. RESULTS: The microvessel density (MVD) and lymphatic vessel density (LVD), according to the CD105 and D2-40 expressions of the endoscopic biopsies, showed a statistically significant correlation with the surgical biopsies. The MVD via CD105 a showed statistically significant correlation with the histologic differentiation, T-stage, nodal metastasis and stage in the endoscopic biopsies and surgical biopsies, respectively. The lympathic vessel density (LVD) via D2-40 showed a statistically significant correlation with T-stage, nodal metastasis and stage in the endoscopic biopsies. The expressions of VEGF-A and VEGF-D showed a statistically significant correlation with the MVD and LVD. CONCLUSION: The MVD, as determined by the CD105 expression and the LVD as determined by the D2-40 expression may be useful markers for predicting the invasiveness with using a pre-operative endoscopic biopsy of stomach cancer.

Correlation between high mobility group protein 1,VEGF-C/D expressions and lymph node metastasis in colon cancer / 第三军医大学学报

Objective To discuss the correlation between the expressions of high mobility group protein box 1(HMGB1),VEGF-C/D and lymph node metastasis in colon cancer.Methods Forty-five colon cancer samples were stained by immunohistochemical method for VEGF-C/D,HMGB1.The correlations of VEGF-C/D,HMGB1 expressions and lymph node metastasis were analyzed statistically.Results Positive HMGB1 expression was in 33 specimens,lymph node metastasis was in 27 specimens with 23 specimens of positive HMGB1 and non-lymph node metastasis was in 18 specimens with 10 specimens of positive HMGB1.Positive VEGF-C expression was in 27 specimens with 20 in lymph node metastasis.The expression of HMGB1 was consistent with VEGF-C expression,and HMGB1 and VEGF-C expressions were closely correlated with lymph node metastasis,but not with age,sex,cellular differentiation.Conclusion HMGB1 and VEGF-C expression may become predictor to the prognosis of colon cancer patients.

Study on the Relationship between Expressions of VEGF-C, VEGF-D and Metastasis in Papillary Carcinomas of Thyroid / 中国医师杂志

Objective To explore the relationship between expressions of VEGF-C, VEGF-D and metastasis in papillary carcinoma of the thyroid. Methods Immunohistochemical method was used to detect the microvessel density(MVD) and expressions of VEGF-C and VEGF-D protein in 20 samples of nodular goiter and 115 samples with papillary carcinoma of the thyroid. Results The positive rates of VEGF-C and VEGF-D protein in nodular goiter were 15.0% and 20.0% respectively, and those in papillary carcinoma of the thyroid were 87.0% and 72.2%, respectively. The intratumour MVD in nodular goiter and papillary carcinoma of the thyroid was 15.2?6.7 and 21.5?8.5 respectively. The expressions of VEGF-C, VEGF-D protein and MVD in papillary carcinomas of the thyroid were significantly higher than those of nodular goiter. The expressions of VEGF-C and VEGF-D protein were closely related to lymph node metastasis of papillary carcinoma of the thyroid(P

Correlation between VEGF-C/D expressions in tumor associated macrophages and lymph node metastasis in colon cancer / 第三军医大学学报

Objective To discuss the correlation between the VEGF-C/D expressions in tumor associated macrophage (TAM) and lymph node metastasis in colon cancer. Methods Forty-five colon cancer samples proven pathologically to be adenocarcinoma were stained by immunohistochemical method for VEGF-C/D and CD68. The correlation of VEGF-C/D expressions, macrophage counting and lymph node metastasis were analyzed statistically. Results The expressions of VEGF-C/D were detected in TAMs. VEGF-C expression was obviously higher in the samples with lymphatic metastasis. VEGF-C expression in colon cancer was related to the number of TAMs. Conclusion TAMs are important in the lymph node metastasis, because they can express VEGF-C/D and affect the lymphangiogenesis of colon cancer.

THE EXPRESSIONS OF VEGF-D AND VEGFR-3 IN COLON CARCINOMA AND THEIR ROLE IN LYMPHATIC METASTASIS OF CARCINOMA / 解剖学报

Objective To investigate the role of vascular endothelial growth factor D(VEGF-D) and vascular endothelial growth factor receptor 3(VEGFR-3) in lymphangiogenesis and lymphatic metastasis of colon carcinoma by observing the expression of VEGF-D and VEGFR-3,and calculated lymphatic vessel density(LMVD) in colon carcinoma. Methods The expressions of VEGF-D and VEGFR-3 were observed by SP immunohistochemistry in 55 colon carcinoma samples of different stages and differentiation degrees.LMVD in colon carcinoma was calculated by using Podoplanin as the specific marker of lymphatic endothelium. Results The positive expression of VEGF-D in colon carcinoma(54.5%) was higher than that in peritumoral tissues(P