1.Vascular Endothelial Growth Factor - Its Relation to Neovascular ization and Their Significance as Prognostic Factors in Renal Cell Carcinoma.
Ki Hak SONG ; Jisun SONG ; Goo Bo JEONG ; Jung Min KIM ; Soon Hee JUNG ; Jaemann SONG
Yonsei Medical Journal 2001;42(5):539-546
Angiogenesis is a series of processes that include endothelial proliferation, migration and tube formation. Vascular endothelial growth factor (VEGF) is regarded as a potent mediator of angiogenesis, vascular permeability and tumor cell growth in renal cell carcinoma. This study was designed to evaluate the expression of VEGF and the microvessel count (MVC) and to determine their prediction efficacies for prognosis in renal cell carcinoma. The relationship between the expression of VEGF and MVC were evaluated immunohistochemically in 50 patients with renal cell carcinoma who received a radical nephrectomy at Wonju Christian Hospital between 1989 and 1997. Microvessels were identified by immunostaining endothelial cells for CD-31 antigen. The mean follow-up was 96 months (3 - 133 months). Overall 5-year survival rate was 71.5%. VEGF was expressed in the tumor cell cytoplasm. Of the 50 tumors, 23 (46%) were weak to strongly positive for VEGF but 27 (54%) were unreactive. The respective 5-year survival rates for patients with positive and negative expressions of VEGF were 70% and 73% (p > 0.05). The overall mean MVC was 13.4 in a 400x field. Mean MVCs were significantly higher in VEGF-positive tumors (17.6 +/- 12.1) than in VEGF-negative tumors (9.9 +/- 5.4), and the MVCs of the high vascular density group and the low ascular density groups were significantly different. The 5-year survival rates of patients with high vascular density and low vascular density were 59% and 86%. The median survival period for patients with MVCs higher than or equal to 10 vessels/field was 85 months, whereas for those with MVCs lower than 10 vessels/field the median survival time was 102 months. These results suggest that MVC may be a better prognostic factor in renal cell carcinoma than the expression of VEGF.
Adult
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Aged
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Carcinoma, Renal Cell/*blood supply/*metabolism
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Endothelial Growth Factors/*metabolism
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Female
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Human
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Kidney Neoplasms/*blood supply/*metabolism
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Lymphokines/*metabolism
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Male
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Middle Age
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Neovascularization, Pathologic/*pathology
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Prognosis
2.Correlation of multislice spiral CT findings with vascular endothelial growth factor expressions and microvessel density in renal cell carcinoma.
Jun XIA ; Ping LUO ; Hui WANG ; Yi LEI ; Pin-ni LIU ; Hua-jian XU ; Zhi-gang CHEN
Journal of Southern Medical University 2006;26(5):629-631
OBJECTIVETo study the correlation of multislice spiral CT features and vascular endothelial growth factor (VEGF) expressions and microvessel density (MVD) in renal cell carcinoma (RCC).
METHODSFourth-seven patients with pathologically confirmed RCC were examined by multislice spiral CT, and VEGF expressions and MVD of the RCC and the adjacent normal tissues were determined by immunohistochemistry with specific monoclonal antibodies.
RESULTSVEGF expression and MVD in the RCC and adjacent normal tissues increased with the pathological grades of RCC (P<0.05), VEGF expression was found to significantly correlate with MVD (r=0.67, P<0.01). The positive expression of VEGF and MVD were associated with the findings by multislice spiral CT scan of tumor size, intratumor necrosis, cystic degeneration, intensity signal, lymph node metastases, invasion of the renal vein or inferior vena cava, and invasion of the adjacent organs or distant metastases (P<0.01).
CONCLUSIONMultislice spiral CT findings can be indicative of the histopathology of RCC, and some CT findings are closely correlated with MVD and VEGF expressions in RCC, which may help evaluate the biological behavior and malignancy of the tumor and predict tumor invasion and metastasis.
Adult ; Aged ; Carcinoma, Renal Cell ; blood supply ; diagnostic imaging ; metabolism ; Female ; Humans ; Kidney Neoplasms ; blood supply ; diagnostic imaging ; metabolism ; Male ; Microcirculation ; Middle Aged ; Tomography, Spiral Computed ; methods ; Vascular Endothelial Growth Factor A ; biosynthesis
3.Correlation of microvascular density and clinicopathological factors in different subtypes of renal cell carcinoma.
Yan-hui ZHANG ; Qing YANG ; Wei CUI ; Yan-xue LIU ; Su-xiang LIU ; Xin YAO
Chinese Journal of Oncology 2010;32(2):117-122
OBJECTIVEThe aim of this study was to evaluate the expressions of CD34, CD31 and microvessel density (MVD) in different subtypes of renal cell carcinoma (RCC) as well as the relationship between MVD and clinicopathological factors.
METHODSExpressions of CD31 and CD34 were detected in 149 patients with RCC using SP immunohistochemical staining. The MVD was studied by Weidner's method.
RESULTSThe expressions of CD31 and CD34 in the clear cell renal cell carcinoma (CCRCC) (98.35 +/- 55.05, 128.04 +/- 46.44) were significantly higher than those in chromophobe renal cell carcinoma (ChRCC) (30.70 +/- 17.72, 48.55 +/- 14.09) and papillary renal cell carcinoma (PRCC) (21.60 +/- 9.38, 38.12 +/- 10.98) (P < 0.01). The MVD value marked by CD31 (30.70 +/- 17.72, 21.60 +/- 9.38) was much lower than that marked by CD34 (48.55 +/- 14.09, 38.12 +/- 10.98) between ChRCC and PRCC (P < 0.01). Smaller and immatured microvessels and even single endothelial cells could be clearly seen. The MVD values marked by CD31 and CD34 were negatively correlated with the pathological grades (r(CD34) = -0.618, P < 0.01; r(CD31) = -0.442, P < 0.01) and clinical stages (r(CD34) = -0.283, P < 0.05; r(CD31) = -0.256, P < 0.05) in CCRCC. But no association was found in non-CCRCC (P > 0.05).
CONCLUSIONMVD is significantly correlated with different types of endothelial labeling. The microvascular endothelial cells could be shown clearly by its related antigen labeling such as CD34 and CD31. CD34 is more sensitive than CD31. The MVD of CCRCC is significantly higher than that in non-CCRCC. The expressions of CD31 and CD34 are not correlated with tumor grade and stage in ChRCC and PRCC, while there is a negative correlation in CCRCC.
Adult ; Aged ; Aged, 80 and over ; Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; blood supply ; classification ; metabolism ; pathology ; Endothelial Cells ; metabolism ; Female ; Humans ; Kidney Neoplasms ; blood supply ; classification ; metabolism ; pathology ; Male ; Microvessels ; metabolism ; pathology ; Middle Aged ; Neoplasm Staging ; Platelet Endothelial Cell Adhesion Molecule-1 ; metabolism
4.Detection and clinical significance of platelet derived growth factor-BB and microvessel density in clear cell renal cell carcinoma.
Li-feng QI ; Dan SUN ; Jian-hua ZHENG ; Jun DU ; Xin YAO
Chinese Journal of Oncology 2013;35(9):672-677
OBJECTIVETo investigate the expression of platelet derived growth factor-BB (PDGF-BB) and microvessel density (MVD) marked with CD34 in clear cell renal cell carcinoma (CCRCC) and explore their relevance to clinicopathologic features and prognoses of patients.
METHODSExpressions of PDGF-BB and CD34 in the tissue samples of 100 clear cell renal cell carcinomas were detected by immunohistochemical (IHC) SP staining. The microvessel density (MVD) was counted using Weidner's method. For PDGF-BB assessment, the staining intensity and the proportion of positive tumor cells were analyzed. Staining was considered immunoreactive when brown granules were identified in the cytoplasm or nuclei of tumor cells. Staining intensity and the proportion of positively stained tumor cells in lesions was scored for further analysis. Statistical analysis was performed using the software SPSS 18.0.
RESULTSThe MVD value marked by CD34 in the 100 cancer tissues was (105.49 ± 37.95) profiles/HPF. The median value of MVD in the entire cohort was used as the cut-off point for low MVD group (42 cases) and high MVD group (58 cases). The MVD of the low and high MVD groups was (75.12 ± 22.41) profiles/ HPF and (135.86 ± 22.91) profiles/HPF, respectively, with a statistically significant difference (P < 0.001). MVD was significantly correlated with the tumor T staging, histopathological grading and postoperative metastasis in CCRCC (P < 0.05, respectively). Among the 100 CCRCC cases, there were 38 cases with low PDGF-BB expression and 62 cases with high PDGF-BB expression, and the expression of PDGF-BB was significantly correlated with tumor diameter, T staging, histopathological grading and postoperative metastasis in the CCRCC (P < 0.05, respectively). Kaplan-Meier survival analysis showed that the cancer specific survival (CSS) in CCRCC patients with high expression of MVD and PDGF-BB was significantly better than that in the group with low MVD and low PDGF-BB expression (P < 0.001, respectively). Expression of PDGF-BB protein was positively associated with the MVD assessed by Spearman's correlation and factor analysis (r = 0.461, P < 0.001).
CONCLUSIONSignificantly increased MVD and PDGF-BB expression detected in CCRCC patients indicate a better tumor grading and staging, and a longer survival time.
Antigens, CD34 ; metabolism ; Carcinoma, Renal Cell ; blood supply ; metabolism ; pathology ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; blood supply ; metabolism ; pathology ; Male ; Microvessels ; metabolism ; pathology ; Middle Aged ; Neoplasm Grading ; Neoplasm Metastasis ; Neoplasm Staging ; Proto-Oncogene Proteins c-sis ; metabolism ; Treatment Outcome
5.Correlation between lymphangiogenesis and clinicopathological parameters in renal cell carcinoma.
Ilyas OZARDILI ; Mehmet Emin GULDUR ; Halil CIFTCI ; Muharrem BITIREN ; Adem ALTUNKOL
Singapore medical journal 2012;53(5):332-335
INTRODUCTIONLymphangiogenesis has been reported to be important in the prognosis of several tumours. The aim of this study was to assess the correlation between lymphangiogenesis and clinicopathological prognostic parameters in patients with clear cell renal cell carcinoma.
METHODS62 patients with renal cell carcinoma were included in the study. The D2-40 antibody, assessed immunohistochemically for each patient, was used as a marker. Light microscopy was used to determine the presence of intratumoral lymphatic vessels (ILVs) and the number of peritumoral lymph vessels (PLVs)/mm2 or PLV density (PLVD). Correlation between the numbers and the Fuhrman nuclear grade, tumour stage, distant metastasis status, presence of lymph node metastasis and lymphovascular invasion was assessed.
RESULTSA significant correlation was found between the presence of ILVs and distant metastasis (p = 0.033) and lymph node metastasis (p = 0.024). However, no significant correlation was found between the Fuhrman nuclear grade (p = 0.553), tumour stage (p = 0.464) and lymphovascular invasion (p = 0.242). Mean PLVD was 20.8, and no significant difference was found between the patients with PLVD below average and those with PLVD above average in terms of distant metastasis (p = 0.337), lymph node metastasis (p = 0.792), the Fuhrman nuclear grade (p = 0.566), tumour stage (p = 0.795) and lymphovascular invasion (p = 0.942).
CONCLUSIONWe found a significant correlation between ILVs and lymph node and distant metastases in patients with renal cell carcinoma.
Adult ; Aged ; Aged, 80 and over ; Antibodies, Monoclonal, Murine-Derived ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; blood supply ; metabolism ; secondary ; Disease Progression ; Female ; Follow-Up Studies ; Humans ; Kidney Neoplasms ; blood supply ; metabolism ; pathology ; Lymph Nodes ; pathology ; Lymphangiogenesis ; Lymphatic Metastasis ; Lymphatic Vessels ; pathology ; Male ; Middle Aged ; Neoplasm Staging ; Prognosis ; Retrospective Studies ; Young Adult
6.Effect of silencing heparanase on the biological behavior of gastric carcinoma in nude mice.
Na HUAI ; Hong YU ; Xiu-mei MA
Chinese Journal of Oncology 2010;32(9):645-649
OBJECTIVETo investigate the effects of silencing heparanase (HPA) on growth, angiogenesis and metastasis of human gastric carcinoma transplanted in nude mice.
METHODSHuman gastric carcinoma SGC-7901 cells and those cells with silenced HPA (gastric carcinoma SGC-7901-HPA(-)) were separately transplanted subcutaneously in 6 nude mice. The time, size and speed of tumor growth were recorded. RT-PCR and Western-blot were used to detect the expression of HPA mRNA and protein in the subcutaneous tumors of the two groups. Immunohistochemical staining was used to detect microvessel density (MVD) in the subcutaneous tumors of the two groups. Cells of the subcutaneous transplanted tumors of the two groups were separately injected into the peritoneal cavity of nude mice, 6 mice each. The growth of metastatic tumors in nude mice was observed.
RESULTSHuman gastric carcinoma SGC-7901 cells and SGC-7901-HPA(-) cells were subcutaneously inoculated in nude mice, and tumors appeared at 4 days and 7 days after inoculation, respectively. The MVD was (20.69 ± 1.20)/HP and (11.35 ± 1.94)/HP, respectively (P < 0.05). The expressions of HPA mRNA and protein of the subcutaneously transplanted SGC-7901-HPA(-) tumor were decreased. Four voluminous metastatic tumors caused by SGC-7901 cells occurred in 3 mice in the liver, right kidney, omentum and intestine. Two smaller abdominal metastatic tumors of SGC-7901-HPA(-) cells were found in the liver and right kidney.
CONCLUSIONSilencing HPA can inhibit the tumor growth, angiogenesis and metastasis of human gastric cancer in nude mice. It suggests that HPA might become a new target for prevention and treatment of gastric cancer.
Adenocarcinoma ; blood supply ; enzymology ; genetics ; pathology ; secondary ; Animals ; Cell Line, Tumor ; Gene Silencing ; Glucuronidase ; biosynthesis ; genetics ; physiology ; Humans ; Kidney Neoplasms ; secondary ; Liver Neoplasms ; secondary ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Microvessels ; pathology ; Neoplasm Transplantation ; Neovascularization, Pathologic ; RNA, Messenger ; metabolism ; Stomach Neoplasms ; blood supply ; enzymology ; genetics ; pathology