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Original Articles
- Correlation between Tumor Angiogenesis and Metastasis in Invasive Breast Carcinoma.
- Nam Hoon Kim, Moon Hyang Park
- Korean J Pathol. 1995;29(6):740-745.
- 1,474 View
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Abstract
PDF - 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.
- A Study on the Tumor Angiogenesis and Expression of Cytokine and Growth Factors in the Prostatic Carcinoma.
- Sung Chul Lim, Ho Jong Jeon
- Korean J Pathol. 1996;30(8):671-679.
- 1,467 View
- 16 Download
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Abstract
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- There is considerable experimental evidence to indicate that tumor growth is dependent on angiogenesis. However, we do not understand how the angiogenic activity is initiated by a given tumor. There is a clear distinction between a stage without neovascularization, which correlates with a paucity of metastases, and a stage in which increasing neovascularization correlates with a rising rate of metastasis. The authors therefore asked whether the extent of angiogenesis in human prostatic carcinoma is correlated with the tumor grades or some growth factors. To investigate how tumor angiogenesis correlates with tumor aggressiveness, the authors counted microvessels within the various grades of invasive prostatic carcinomas of 44 patients and the nodular hyperplasias of 10 patients. Highlighting of the vessels by immunohistochemical staining for factor VIII-related antigen and assessment of the tumor aggressiveness by the degree of expression of some growth factors(transforming growth factor-alpha, and beta, epidermal growth factor), tumor necrosis factor-alpha and tumor grading(Gleason's score) were done. As a result, both microvessel counts and the expression of growth factors and tumor necrosis factor correlated with tumor grades. In conclusion, the number of microvessels per 200 X fields in the areas of most intense neovascularization in a prostatic carcinoma may be a predictor of the patient's prognosis. Therefore, assessment of tumor angiogenesis may prove valuable in selecting patients with prostatic carcinoma, especially small needle biopsy, for aggressive therapy.
- Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor.
- Jeong Yun Shim, Ho Guen Kim, Tai Seung Kim
- Korean J Pathol. 1997;31(1):23-33.
- 1,829 View
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Abstract
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- Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.
- The Significance of the Expression of p53, E-cadherin, nm23, CD44, and Tumor Angiogenesis in Colorectal Adenocarcinoma.
- Sung Suk Paeng, Hee Jin Chang, Jung Il Suh
- Korean J Pathol. 1997;31(4):314-325.
- 1,510 View
- 11 Download
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Abstract
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- Many oncogenes and tumor supressor genes have been identified and studied in colorectal carcinoma. Among them, p53 is a tumor supressor gene and its mutation is frequently noted in human tumors. E-cadherin is a cell adhesion molecule and associated with tumor differentiation. CD44 is a cell surface glycoprotein that plays a role in cell migration and metastasis. nm23 is a gene known to lower metastatic potential of tumors and has been proposed to be a metastasis supressor gene. Tumor angiogenesis is required for the expansion of the primary tumor and metastasis and its degree is related to the potential of malignancy. We studied the expression of p53, E-cadherin, nm23, CD44 and tumor angiogenesis in 36 cases of colorectal adenocarcinomas. They were compared with previously known prognostic factors such as the stage, tumor size, depth of invasion, differentiation, presence of lymphatic or venous invasion, the lymph node and distant metastasis. The results were as follows. 1) The expression of p53 was not significantly associated with any prognostic factors. 2) The expression of E-cadherin was significantly associated with tumor differentiation. In the well differentiated adenocarcinomas, its expression was higher than in the poorly differentiated adenocarcinoma. 3) The expression of nm23 was also significantly associated with tumor differentiation. In carcinoma with lymph node metastasis, the expression of nm23 was reduced, but statistically it was not significant. 4) The expression of CD44 was higher in tumors with lymph node metastasis than in tumors without lymph node metastasis, but it was not statistically significant. 5) The degree of microvessel density was significantly associated with lymphatic invasion. According to the above results, the expression of E-cadherin and nm23 are related to the differentiation of the tumor and tumor angiogenesis is related to the lymphatic invasion of the colorectal adenocarcinoma.
- Correlation of Tumor Angiogenesis and nm23-H1 Expression with Lymph Node Metastasis in Proper Muscle Gastric Cancer.
- Eun Sook Nam, Gu Kang, Hyung Sik Shin, Young Eui Park
- Korean J Pathol. 1997;31(5):410-416.
- 1,643 View
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Abstract
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- We studied clinicopathologic features of 44 cases of PM (proper muscle) gastric cancer, correlated the lymph node metastasis and found the result of immunohistochemical staining for tumor angiogenesis using antibodies to Factor VIII-related antigen and nm23-H1, known as meatastasis inhibitory substance. The results were as follows: 1) The average age of these 44 cases of PM gastric cancer was 55.1 years old (range 35-81). The ratio of male to female was 2.2 : 1. The tumor was located at the antrum of stomach in 72.7% of the cases. The average size of the tumor was 4.1 cm (range 0.6-9). The gross features were comprised of Borrmann type I (6.8%), II (29.6%), III (56.8%), IV (6.8%), respectively. The microscopic type was a diffuse type in 70.5% and an intestinal type in 29.5%. There were lymph node metastasis in 25 of the 44 cases (56.8%). 2) The microvessel count was higher in the lymph node positive group (average 69.3) than in the lymph node negative group (average 45.6) (P=0.004). There was a higher microvessel density in diffuse type, over 4 cm of tumor size, proximally located tumor, older than 50 years, Borrmann type II and IV, but there was no statistically significant correlation. 3) The more decreased expression of nm23-H1 was found in the lymph node positive group (56.0%) than in the lymph node negative group (31.6%), but showed no statistical significance (P=0.0142). There was no significant correlation between the expression of nm23-H1 and the other clinicopathologic factors. We suggest that the microvessel count of the tumor angiogenesis may be a prognostic factor for predicting lymph node metastasis and also help to determine the therapeutic modalities of PM gastric cancer.
- Tumor Angiogenesis in Renal Cell Carcinoma.
- Ji Shin Lee, Jong Jae Jung, Chang Soo Park
- Korean J Pathol. 1999;33(11):1055-1060.
- 1,474 View
- 19 Download
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Abstract
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- Angiogenesis is essential for the growth of solid tumors. Microvessel counts, which represent a measure of tumor angiogenesis, have been correlated with the overall survival of patients with a variety of malignancies. However, the significance of angiogenesis in renal cell carcinoma remains controversial. To determine whether angiogenesis correlates with prognosis of patients with renal cell carcinoma, we counted the microvessels within the primary tumors and compared their numbers with patients' prognosis. Tumor specimens from 42 patients were investigated. Microvessels were stained with anti-CD34 and anti-factor VIII-related antigen monoclonal antibodies. Significant correlation between microvessel counts for two antibodies was observed (r=0.875, p<0.01), although microvessel counts for CD34 were approximately two times higher. Microvessel counts were higher in clear cell than in non-clear cell carcinoma (p<0.05). These results suggest that immunostaining with anti-CD34 antibody may provide a more sensitive and accurate measure of tumor angiogenesis. There was no correlation between microvessel counts and nuclear grade, or TNM stage. In univariate analyses, nuclear grade and TNM stage were significantly associated with patient survival (p<0.01). But further studies on tumor angiogenesis of renal cell carcinoma are needed before it can be adopted as a prognostic marker.
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