Relationship of the expression of transforming growth factor,vascular endothelial growth factor with angiogenesis in thyroid cancer / 中国基层医药

Objective To investigate the relationship of the expressions of transforming growth factor ?_1(TGF?_1),vascular endothelial growth factor(VEGF) with angiogenesis in thyroid cancer.Method TGF?_1,VEGF and microvessel countt(MVC) were detected by immunohistochemical method in 46 thyroid cancer specimens.Results The mean MVC was significantly higher in tumors with positive TGF?_1 or VEGF than in tumors with negtive TGF?_1 or VEGF[(26.18?4.05) vs (20.13?4.29) for TGF?_1 and (25.82?3.61) vs (19.65?6.32) for VEGF,P

Expression of Thymidine Phosphorylase in Human Gastric Carcinoma

PURPOSE: Angiogenesis plays an important role in the growth and metastasis of solid tumors. It has been recently reported that thymidine phosphorylase (dThdPase) is identical to platelet-derived endothelial cell growth factor. In this study, we analyzed the correlation between dThdPase activity and neovascularization, and also determined their prognostic significance by enzyme-linked immunosorbent assay (ELISA) and immunohistochemical staining in patients with gastric carcinoma. METHODS: The medical records of 57 patients with gastric carcinoma who underwent radical gastrectomy were retrospectively reviewed. Primary tumors were studied by immunohistochemical staining with anti-PD-ECGF/dThdPase and anti- CD34 monoclonal antibodies. The dThdPase activity level was also analyzed by ELISA. Microvessels were assessed by immunostaining endothelial cells for CD34. We counted the number of microvessels in the tumors of the patients. RESULTS: The dThdPase activity of tumor tissues (82.4+/-66.2 unit/mg protein) was significantly higher than that of normal mucosas (8.9 +/- 18.2 unit/mg protein) (P < 0.0001). Immunohistochemical staining with anti-dThdPase and anti-CD34 monoclonal antibodies was performed in 57 gastric carcinoma tissue samples. Positive dThdPase expression was observed in 24 (42.1%) tumors. The average number of cells expressing CD34 was significantly higher in the dThdPase- positive carcinomas (44.4+/-15.3) than in the dThdPase- negative carcinomas (30.7+/-15.8)(P<0.003). The expression of dThdPase was significantly associated with the intratu moral microvessel counts (P=00005). The patients with dThdPase-positive carcinoma showed a significantly worse prognosis than those with dThdPase-negative carcinoma (P=0.034). CONCLUSION: These results suggest that dThdPase plays a role in the promotion of angiogenesis, and that it is a possible candidate as a prognostic factor in human gastric carcinomas.

Expression of Vascular Endothelial Growth Factor and Interleukin-6 in Multiple Myeloma / 대한혈액학회지

BACKGROUND: Vascular endothelial growth factor (VEGF) is a multifunctional cytokine involved in angiogenesis as selective mitogen for endothelial cells as well as potent permeability factor. And interleukin-6 (IL-6) is also known to be a growth factor of myeloma cells. To determine the role of angiogenesis, VEGF and IL-6 in the patients with multiple myeloma, the relationship between the level of VEGF expression, microvessel count (MVC), IL-6 expression in the bone marrow specimen of multiple myeloma patients and stage, response, survival duration were evaluated in 18 patients with multiple myeloma who underwent bone marrow biopsy. METHODS: VEGF expression, MVC and IL-6 expression were assessed by immunohistochemical stain with polyclonal antibody to VEGF, factor VIII related antigen and IL-6 respectively. RESULTS: VEGF expression was higher in multiple myeloma than that of control (61.4+/-34.4% vs 19.0+/-25.9%, P<0.001), and MVC was also higher in multiple myeloma than that of control (11.7+/-6.1 vs 6.2+/-3.8, P=0.005). IL-6 was expressed in 66.7% of multiple myeloma but not in control (P<0.001). Between high VEGF expression group and low VEGF expression group, there were no significant differences in the stage, response or survival. There were no significant differences between hypervascular group and hypovascular group. Also IL-6 expression was not a prognostic indicator. After treatment, VEGF expression, MVC and IL- 6 expression were decreased in the responder, but these differences were not statistically significant (P=0.23, P=0.07, P=0.06), probably due to limited number of cases. CONCLUSION: VEGF, angiogenesis and IL-6 can play a role in the pathogenesis of multiple myeloma. But we cannot confirm the prognostic role of those parameters. Further study with more cases in longer duration as well as prospective study would be necessary for the establishment of relationship between VEGF expression, neovascularization, IL-6 expression and disease severity and prognosis of multiple myeloma.

Vascular Endothelial Growth Factor (VEGF) Expression and Angiogenesis in Gastric Cancer

PURPOSE: This study was designed to evaluate the angiogenic activities of gastric cancer tissue and adjacent normal gastric tissue and to analyze the correlations between the clinicopatholoic factors of gastric cancer and tumor angiogenic activity. METHODS: Sets of both tumor tissue and adjacent normal gastric tissue were sampled from 49 patients with gastric cancer at the time of gastrectomy. Each specimen was evaluated for the expression of VEGF mRNA by reverse transcriptase polymerase chain reaction (RT-PCR). For the microvessel count of each tissue sample, immunohistochemical staining was done using antiCD31 antibody. As a control group, 10 paraffin blocks of normal gastric tissue from patients with benign disease were selected and stained with the same antibody in order to count the microvessels. RESULTS: The microvessel count of the tumor tissue was higher than that of normal tissue, with a mean+/-SD of 74.10+/-30.33 and 24.69+/-10.11, respectively (p<0.001). The microvessel count of the control group was 23.40+/-6.77 and was not significantly different from that of normal tissue samples taken from patients with gastic cancer. VEGF/beta actin ratios measured from the results of RT-PCR were 0.70+/-0.32 in tumor tissue and 0.51+/-0.26 in normal tissue (p<0.001). In each tissue sample, there was a significant correlation between the microvessel count and VEGF/beta actin ratio (p<0.01 in the tumor tissue, p<0.05 in normal tissue). Micro-vessel count of tumor tissue was related with sex and types of Lauren's classification (p<0.05, p<0.01, respectively). The VEGF/beta actin ratio of tumor tissue was related to sex and degree of vascular invasion of tumor cells (p<0.05). Other clinicopathologic factors, such as age, histologic type, TNM stage, tumor depth, lymph node metastasis, and perineural invasion, were not associated with the degree of microvessel count and the level of VEGF mRNA expression. CONCLUSION: Gastric cancer shows marked angiogenic activity and the angiogenesis is related to some clinicopathologic factors. These results suggest that the clinical application of antiangiogenic agents may have a role in the treatment of gastric cancer.

Angiogenesis and Proliferating Cell Nuclear Antigen Index in Non-small Cell Lung Carcinomas / 대한암학회지

PURPOSE: This study aimed to determine the relationship between angiogenesis and tumor cell proliferation evaluated by proliferating cell nuclear antigen (PCNA) in non-small cell lung carcinomas (NSCLCs) and to investigate the prognostic significance of the factors in them. MATERIALS AND METHODS: Immunohistochemical staining for factor VIII related antigen, vascular endothelial growth factor (VEGF) and PCNA was performed using paraffin embedded blocks of 57 NSCLC cases. The results were correlated with some clinicopathologic parameters, including age, sex, TNM-T status, TNM-N status, stage, and histologic type. RESULTS: Microvessel count (MC) was higher in squamous cell carcinoma group than in non-squamous cell carcinoma one (18.4+/-7.3 vs 14.6+/-9.9, p=0.043). PCNA index was higher in lymph node metastasis group than in non-metastasis one (42.1+/-8.9% vs 36.4+/- 14.6%, p=0.043). But the factors were not correlated with other clinicopathologic parameters. The relationship between VEGF expression and MC was significantly recognized (p=0.02), but that between VEGF expression and PCNA index was not. MC was positively correlated with PCNA index (r=0.547, p=0.005). CONCLUSION: These findings suggest that both MC and PCNA index can be acted as useful indicators of prognosis in NSCLC, but tumor cell proliferation in NSCLC may be more concerned with any growth factor other than VEGF.

Microvessel Count and Overexpression of p53 in Early Colorectal Cancer / 대한암학회지

PURPOSE: Angiogenesis, playing a critical role in tumor growth, development, and metastatic process, is alleged to be related to the prognostic factors and patient's survival of the colo-rectal cancer. The p53 gene, present in short arm of chromosome 17, is involved in multistep colo-rectal carcinogenesis. The correlation of p53 gene and angiogenesis has been recently reported. So, we designed to assess (1) the rate of p53 overexpression, (2) the prognostic significance of microvessel count, and (3) the relationship of p53 overexpression and angiogenesis in early colo-rectal cancer(ECC) patients. MATERIAL AND METHODS: The study material included 68 ECC from 65 patients, 40 mucosal (m-ECC) and 28 submucosal ECCs (sm-ECC). Immunostainings against p53 and factor VIII-related antigen were done and the results were analyzed with respect to tumor depth, site, and differentiation. And also the correlation between p53 overexpression and microvessel counts(MVC) was performed. RESULT: The rate of p53 overexpression was higher in sm-ECC than in m-ECC (p < 0.05). The rate of p53 overexpression was highest in sigmoid colon and statistically significantly different compared with other sites. The differentiation of the tumor was closely correlated with p53 overexpression and the poorer the differentiation, the more overexpression of p53 (p<0.05). There was no significant difference between MVCs of m-ECC and sm-ECC (27.2+/-5.5 and 29.8 +/-6.0,respectively). However, MVC were higher in sigmoid colon than in any other sites (p<0.05). MVC did not show significant correlation with tumor differentiation or p53 overexpression. CONCLUSION: These data indicate that p53 overexpression is correlated with tumor depth and differentiation but not MVC. The significance of higher MVC and p53 overexpression in sigmoid colon are reserved for further studies.

Microvessel Quantitation and Assessment of its Utility by CD34 Staining in Invasive Breast Carcinoma

Tumor angiogenesis, the development of new blood vessels by tumor, is a widely observed phenomenon associated with the growth of human solid tumors. To investigate how tumor angiogenesis correlates with other prognostic features i.e. menopause status, tumor size, lymph node metastasis, mitosis, angioinvasion, estrogen receptor (ER), p53 protein expression, histologic grade and clinical stage, we counted microvessels by immunohistochemistry using antibody for CD34 antigen in 56 cases of invasive breast carcinoma (27 with and 29 without axillary lymph node metastases) and 20 cases of non-inflammatory benign breast lesion. CD34 antigen is expressed on the surface of hematopoietic progenitor cells and more sensitively expressed than factor VIII in vascular endothelial cells. Microvessel count (MVC) was performed at a single hot field of 200x magnification (0.74 mm2 per field). The results are summarized as follows; 1) The mean MVC of invasive carcinoma and benign breast lesion were 92.0+/-54.4 (range, 7-237) and 20.7+/-16.6 (range, 4-73), respectively (p0.05), MVC had a tendency to increase in tumors with axillary LN metastasis or without ER expression. 3) Without correlation with MVC, ER (+), angioinvasion (-) and higher histologic grade correlate to significantly higher mitosis count (p<0.0005). Also, angioinvasion correlate to a significantly higher histologic grade (p<0.05). In conclusion, angiogenesis is related to tumorigenesis, but MVC may not be related to other clinicopathologic factors.

A study of Tumor Angiogenesis in Human Lung Cancerby Immunohistochemical Stain / 결핵

Background: Tumor angiogenesis is the growth of new vessels toward and within tumor. It has been demonstrated that the growth of tumor beyond a certain size requires angiogenesis and it is closely involved in tumor progression and metastasis. The finding that intensity of neovascularization correlates independently with metastasis may lead to identification of patients in whom radical surgery should be supplemented by systemic treatment. Method: We have collected paraffin blocks of bronchoscopic biopsy of patients with non-small cell lung cancer. We highlighted the vessel by staining endothelial cell with JC70 monoclonal antibody(to CD31) immunohistochemically and counted microvessels under 200 X field using light microscopy. Results: 1) The mean microvessel count was 32.7+/-20.8 (9-96) in total 29 cases. 2) There were no correlations between microvessel counts and pathologic cell type, T staging, node metastasis(N) and hematogenous metastasis(M) (p>0.05). 3) The median follow-up duration was 15 months(2-46) and there was no correlation between the microvessel counts and survival rate of lung cancer patients (p>0.05). Conclusion: Tumor angiogenesis seems to be an important prognostic factor suggesting the probability of metastasis. But the microvessel count in the bronchoscopic biopsy specimen was inadequate and very limited. There has been no data about angiogenesis of lung cancer in korea yet. So the study of tumor angiogenesis using resected lung tumor specimen would be demanded.

Correlation between Tumor Angiogenesis and Metastasis in Invasive Breast Carcinoma

Tumor angiogenesis(TA) refers to the growth of new vessels toward and within a tumor. TA is necessary both at the beginning and at the end of the metastatic cascade of events. Recently, experimental evidence suggests that the growth of a tumor beyond a certain size requires angiogenesis. To investigate how tumor angiogenesis correlates with metastases in breast carcinoma, the microvessels were counted (per 200 / field) in the most active areas of neovas-cularization by two investigators. The microvessels within breast carcinoma were highlighted by in imunohistochemical staining for factor VIII-related antigen. Microvessel count(MVC) in node-positive carcinoma(59.66=35) was significantly higher than in node-negative carcinoma(44.76=17)(p=0.009). MVC was also statistically correlated with tumor size and stage, but not with histologic grading, DNA ploidy, or hormonal receptors(estro-gen and progesterone). MVC in invasive breast carcinoma may be one of many prognostic predictors of node-positive breast carcinoma. Assessment of tumor angiogenesis may therefore be valuable in selecting patients with early breast carcinoma for aggressive therapy.