A nodular growth on maxillary gingiva.

A case of angiosarcoma of maxilla is presented. The occurrence of angiosarcoma in the oral cavity is a rare incidence and maxilla is one of the rarest sites to be involved. The purpose of this article is also to emphasize the fact that sometimes small, innocent-looking masses in the oral cavity might actually turn out to be a highly destructive malignant tumor. Hence, a complete radiographic and histopathologic examination is mandatory.

Angiogenesis according to Clinical Forms in Leprosy / 대한피부과학회지

BACKGROUND: Leprosy is a chronic granulomatous infectious disease caused by Mycobacterium leprae. It has recently been reported that various clinical manifestations and treatments of leprosy are associated with increased angiogenesis. However, there are few reports on this topic. OBJECTIVE: This study aims to examine the differences in angiogenesis according to clinical forms of leprosy. METHODS: Thirty-three cutaneous lesions that represented the clinical spectrum of leprosy and 7 normal skins were selected for this study. Clinical forms of leprosy included in this study were 7 cases of tuberculoid (TT), 8 cases of borderline tuberculoid (BT), 8 cases of borderline lepromatous (BL), and 10 cases of lepromatous (LL) leprosy. A total of 40 sections of formalin-fixed, paraffin embedded tissues were investigated for Factor VIII-related antigen (FVIIIRA) expression using immunohistochemical staining. The number of FVIIIRA positive blood vessels in hot spot at a power of x40 was observed by 2 independent dermatologists. RESULTS: The number of vessels ranged from 4 to 12 (mean 8.43+/-2.64) in the normal cutaneous tissues, 23 to 38 (mean 28.86+/-5.46) in the TT, 46 to 71 (mean 56.50+/-8.68) in the BT, 49 to 77 (mean 64.75+/-9.82) in the BL, and 74 to 159 (mean 104.40+/-27.71) in the LL. The mean numbers of vessels in the BT, BL, and LL leprosy lesions were significantly higher than the mean number in the normal cutaneous tissues. Also, an overall increase was observed in the mean number of vessels from TT through BT, BL to LL leprosy lesions. CONCLUSION: We suggest that increased angiogenesis is associated with pathogenesis in leprosy. This study should prove helpful to future research into leprosy treatment.

Cyclooxygenase-2 Inhibitor Delayed the Tumorigenesis of N-Butyl-N-(4-hydroxybutyl)nitrosamine-induced Rat Urinary Bladder Cancer Model / 대한비뇨기과학회지

PURPOSE: Cyclooxygenase-2 (COX-2) plays an important role in promoting cancer cell proliferation and angiogenesis in human bladder cancer. The selective COX-2 inhibitor has antitumor activities in vivo and in vitro in a variety of tumor types. In this study, the antitumor or antiangiogenic effects of selective COX-2 inhibitor on N-butyl-N-(4-hydroxybutyl)nitrosamine-induced rat bladder tumorigenesis were investigated. MATERIALS AND METHODS: Forty male Fischer 344 rats (Control group) were given only 0.05% BBN in water ad libitum, while 40 others (Experimental group) were administered 1,500mug/kg celecoxib once daily through the gavage tube, which started 1 week before the BBN treatment. Ten rats were used as the normal bladder. Ten rats from the control and experimental group were sacrificed 4, 12, 16, and 24 weeks after the start of the BBN treatment. All bladders were evaluated both macroscopically and microscopically. We also measured COX-2 expression, microvessel density (MVD), and vascular endothelial growth factor (VEGF) protein concentrations in the bladder tissues. RESULTS: Macroscopically and microscopically, the incidence of tumor was lower in the experimental group than in the control group from the 12th week to the 24th week. Each incidence of tumor in week 12, week 16, and week 24 was 20%, 50%, and 80% in the control group and 0%, 20%, and 40% in the experimental group, respectively. In both the control and experimental groups, COX-2 expression had a tendency to be concentrated in the cytoplasm of the epithelial cells of the papillary tumor and the endothelial cells adjacent to the vessel the basal layer of bladder. COX-2 and VEGF expression were significantly more decreased in the experimental groups than in the control groups after 4 weeks from the BBN induction (p<0.05). MVD was significantly decreased in the experimental group at week 16 (p<0.05). CONCLUSIONS: The selective COX-2 inhibitor has an inhibitory effect on BBN-induced rat bladder tumorigenesis because of its partially antiangiogenic properties. In the future, the selective COX-2 inhibitor could be expected to play an important role as a chemo-preventive agent and as therapeutic aids in bladder cancer if these inhibitory effects can be reproduced in human bladder tumorigenesis.

Significance of Expression of p16 protein, p53 protein, Ki-67 antigen, and Factor VIII-related Antigen and Their Correlation with the Clinicopathologic Prognostic Factors in Malignant Melanoma / 대한피부과학회지

BACKGROUND: Biologic markers such as the p16 protein, p53 protein and Ki-67 antigen, as well as factor VIII-related antigen have been explored in various malignancies as potential prognostic factors. OBJECTIVE: The aims of this study are to examine the expression of biologic markers and to assess their correlation with conventional clinicopathological prognostic factors in malignant melanoma. METHODS: Immunohistochemical stains for p16, p53, Ki-67 and factor VIII-related antigen were performed in twenty formalin-fixed, paraffin-embedded tissues of primary and metastatic malignant melanomas. We compared the expression of biologic markers with conventional clinicopathologic factors, such as the presence of metastasis, ulceration, Breslow thickness, Clark level and American Joint Commission on Cancer(AJCC) TNM staging. RESULTS: Loss of p16 expression was significantly higher for the metastatic melanomas(90%) than the nonmetastatic(50%). But the results were not correlated with the clinicopathologic prognostic factors. The p53 expression was found in 7/10(70%) of the metastatic melanomas and in 3/10(30%) of the primary melanomas. Statistically, p53 expression was positively correlated with Breslow thickness(p=0.017), Clark level(p=0.003) and TNM staging(p=0.009). Furthermore, statistically significant trends were observed towards increasing expression of Ki-67 with metastatic dissemination(p=0.014), increasing Breslow thickness(p=0.008), Clark level(p=0.012) and TNM staging(p=0.009). Positive correlation was present between TNM staging and factor VIII-related antigen expression(p=0.014). CONCLUSION: p53 protein and Ki-67 antigen may be more useful independent predictors than p16 protein and factor VIII-related antigen in Korean patients with malignant melanoma.

A Case of Nonvenereal Sclerosing Lymphangitis of the Penis

The patient was a 41-year-old healthy man, who developed a tender, cord-like serpiginous mass just proximal to the coronal sulcus for two weeks. He was a sexually active, non-promiscuous, married man. We had taken a biopsy, and noticed the subsiding of the lesion without further treatment. Nonvenereal sclerosing lymphangitis of the penis is a rare self-limiting peculiar disorder involving the lymphatics of the penile sulcus. Clinically, it presents as a cord-like nodular penile lesion with characteristic cartilaginous firmness. Histologically, it is described as hypertrophy and sclerosis of the lymphatic vessel walls with mild inflammatory cellular infiltration, and occasional obstruction of the lymphatic vessel. But, because such features including sclerosis varies according to the time when the biopsy was taken, they are not attributable to all cases. Our case shows the same clinical and pathological features of ‘benign transient lymphangiectasis’. Except for the painful cases, no specific treatments are usually warranted.

Tumor Angiogenesis in Renal Cell Carcinoma

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.

Tumor Angiogenesis in Renal Cell Carcinoma

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.

Correlation of Tumor Angiogenesis and nm23-H1 Expression with Lymph Node Metastasis in Proper Muscle Gastric Cancer

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.

The Significance of the Expression of p53, E-cadherin, nm23, CD44, and Tumor Angiogenesis in Colorectal Adenocarcinoma

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.

Tumor Angiogenesis As a Predictor of Prognosis in Gastric Carcinoma / 대한암학회지

PURPOSE: Angiogenesis is an essential component of tumor growth and proven to be a prognostic factor in breast, cervix, prostate carcinoma and melanoma. This study was designed to define the relationship of microvessel density with overall survival, clinicopathologic data and with other reported prognostic factors in gastric carcinoma. METHODS: We studied resected tumor specimens from thirty-two patients with gastric carcinoma who underwent gastrectomy at Ewha Women's University Hospital from January, 1989 to December, 1991. Specimens were investigated by staining with a monoclonal antibody aganist factor VIII-related antigen, which was localized to vascular endothelium. Correlation between the microvessel count (X200), various clinicopathologic factors, EGFR and p53 were studied. RESULTS: The microvessel count was increased with higher histologic staging. The microvessel count was significantly higher in group with lymph node metastasis than in those without lymph node metastasis (60.7 vs 27.4, p=0.02). In patients with high microvessel count (> or =30), overall survival time was shorter than in those with low count (0.05). The microvessel count was higher in group with recurrence than in those without recurrence (48.1 vs 33.2, p=0.05). CONCLUSION: Microvessel count may be a prognostic indicator in gastric carcinoma but larger scale study should be followed.

A Study on the Tumor Angiogenesis and Expression of Cytokine and Growth Factors in the Prostatic Carcinoma

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.

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.

Isolation and cultivation of microvascular endothelial cells from rat lungs: effects of gelatin substratum and serum

Microvascular endothelial cells from rat lungs were cultured in serum-free medium supplemented with an endothelial growth substance, insulin, hydrocortisone and so on. Five to seven days after plating, cultured cells formed a monolayer. They were identified as endothelial cells by morphology and by positive immunohistochemistry for factor VIII-related antigen, a marker for endothelia cells. Differences between gelatin coated culture plates and plastic culture plates in endothelial cell proliferation were evaluated. Cells plated on uncoated plastic plates had a spindle-shaped morphology and did not express factor VIII-related antigen. Two types of medium, serum-free medium containing endothelial growth substance and basal medium supplemented with 20% fetal calf serum, were also compared in primary culture. In contrast with the serum-free medium, cells cultured in the serum-containing medium showed fibroblast-like morphology and did not express factor VIII-related antigen. These results suggest that a gelatin substratum and serum-free medium containing endothelial growth supplement are necessary for in vitro proliferation of microvascular endothelial cells isolated from rat lungs. The culture method and conditions outlined here allow the proliferation of pure microvascular endothelial cells from rat lungs. It may be useful in studying hematogenous metastasis to the lung and the role of microvascular endothelium in other pulmonary disease.

Factor VIII Related Antigen in Granuloma Pyogenicum / 대한피부과학회지

Using Avidin-Biotin immunoperaxidase method, we investigate the distribution patterns of factor VIII related antigen in various areas of skin lesions of 14 granuloma pyogenicum. and in the skin lesions of 5 capillary hemangioma and 5 normal skin. The results are summarized as follows: 1. Factor VIII related antigen was detected in 9 of 14 cases of granuloma pyogenicum, in 4 of 5 cases of capillary hemangioma, and in 5 of 5 cases of normal skin. 2. In the lesions of granuloma pyogenicum the areas with prominent capillary endothelial cell proliferation had less positivity than the vascular areas. And the areas with relatively large vesels in the lesions of granuloma pyogenicum had similar positivity as capillary hemangioma. 3. The lesions of granuloma pyogenicum and capillary hemangioma had less positivity than the vessels of normal derrnis.