Correlation of VEGF and COX-2 Expression with VM in Malignant Melanomas

OBJECTIVE To investigate the relationship between vascular epithelial growth factor (VEGF) and cyclooxygenase-2 (COX-2) in melanomas and the expressive difference of VEGF and COX-2 between melanomas with and without vasculogenic mimicry(VM).METHODS Sixty cases of malignant melanomas emoeaaea In paraffin were studied. The tumors were divided into a high-grade malignant group and a low-grade malignant group based on their tumor type, atypia and survival time of the patient. Then tissue microarrays were produced from these paraffin-embedded tumor tissues which were stained for VEGF, COX-2 and PAS. The difference in expression between VEGF and COX-2 in the malignant melanomas was compared using a grid-count. In addition, the tumors were also divided into mimicry and non-mimicry groups based on their PAS staining. Then the differences between the PAS positive and negative areas of the 2 groups were compared.RESULTS In malignant melanomas with VM, VEGF and COX-2 expression was less in tumors in which VM was absent, but VEGF, COX-2 expression in high-grade malignant melanomas was higher than that in low-grade grade malignant melanomas. Expression of VEGF was correlated with COX-2 expression.CONCLUSION VM exists in some high-grade malignant melanomas. The differences and relations between VEGF and COX-2 showed that some high-grade malignant melanomas possess a unique molecular-mechanism of tumor metastasis and blood supply.

Effects of Imbalance of Apoptosis and Proliferation on Large Bowel Carcinogenesis in Mice

OBJECTIVE To observe the pattern of changes in the proliferation and apoptosis at different stages of large bowel carcinoma in mice, and to explore the effects of the imbalance of apoptosis and proliferation at different stages of large-intestine carcinogenesis.METHODS An experimental animal model for large intestine carcinogenesis of KUNMING-strain mice was used. The carcinomas were induced by subcuteneous injection of dimethylhydrazine (DMH) and the distribution and density changes of proliferating and apoptotic cells observed through multistages toward cancer formation. The animals were killed in groups at the 12th, 18th, 24th,and 32nd weeks of carcinoma induction. The apoptotic and proliferating cells were labeled separately using TUNEL and PCNA immunohistochemical staining methodsRF, RESULTS In the normal mouse mucosa, all the apoptotic cells were situated in the superficial layers, however, the proliferating cells were situated in the basement layers, and the amount of both were small. In the early stage of carcinoma induction, the proliferation and the apoptotic cells slightly increased in amount, but there were no obvious changes in their ratio. In the medium stage, the densities of both distinctly increased, but there were no obvious changes in the ratio. In the late stage, the densities of the proliferating and the apoptotic cells in the non-carcinoma mucosa were higher than those at other stages. The proliferating cells in the dysplastic mucosa increased progressively with the increasing degree of the lesions. Although the apoptotic cells increased, their changes did not occur with the degree of the lesions. Their ratio showed a decreasing tendency with the degree of the lesions.CONCLUSIONS (①The presence of an imbalance between cell proliferation and apoptosis was confirmed in the course of large intestine carcinogenesis in a mouse model. ②In the early stage of carcinoma induction both proliferation and apoptosis were at a low level; in the medium stage, they were both at a high level; and in the late stage (that is in carcinoma), proliferation was at a very high level, while apoptosis was at a low level. ③The proliferating cells increased progressively with the degree of dysplasia. There were no obvious changes in the apoptotic cells and their ratio to the proliferating cell sshowed a progressively increasing tendency. ④In the stage of cancer formation, the most essential change was the excessive decrease in the ratio of apoptosis to proliferation. These results support the hypothesis of "Cell Selective Proliferation", which was raised by authors previously in a study on human large bowel carcinoma.

Tissue Microarray Study of Vasculogenic Mimicry in Bi-directional Differentiated Malignant Tumors

OBJECTIVE To determine if vasculogenic mimicry (VM) exists in bi-directional differentiated malignant tumors. METHODS The blood supply models for bi-directional differentiated tumors were studied with immunohistochemical and PAS double-staining techniques. New sections were made from 158 paraffin-embedded bi-directional malignant-tumor samples, including melanoma (high malignancy n=30, low malignancy n=30); synoviosarcoma(SS) (high malignancy n=26, low malignancy n=13); acinar rhabdomyosarcoma (All) (high malignancy n=16,low malignancy n=13); malignant mesothelioma (MM) (n=26), and epithelioid sarcoma (ES)(n=4). Tissue microarrays were made. The representative points in the paraffin sections were labeled and two tissue microarrays were made, one included 60 cases of melanoma, and the other included the other tumors. Immunohistochemical staining of the platelet-endothelial cell adhesive molecule(CD31 antigen) and periodic acid Schiff(PAS) staining were conducted. The areas were calculated of vessel-like channels consisting of CD31 antigen-positive tumor cells and of PAS positive materials. The VM was studied using the data obtained. RESULTS Some of these bi-directional tumor cells secreted PAS-positive materials and 0D31 positive materials. The walls of the VM consisted of PAS-positive materials lined with CD31 negative tumor cells with red blood cells inside the channel, whereas the walls of the epithelium-dependent vessels were comprised of CD31 positive materials. The positive areas of CD31 were significantly less than that of PAS (P<0.01). The number of cases with VM in highly malignant tumors was greater than that found in the lowly malignant tumors. CONCLUSIONS Bi-directional differentiated malignant tumor cells have the ability to auto-transform and might interact with the extracellular matrix to form a vessel channel system which mimics blood vessels for transporting blood. That process is called VM. Results in this study show that bi-directional differentiated tumors develop a nutritional supply by VM to satisfy the demand for the rapid growth, and thus acquire higher invasive ability and malignancy.

Primary Renal Malignant Fibrous Histiocytoma Four-Case Report and Review of the Literature

OBJECTIVE To evaluate the diagnosis and treatment for primary renal malignant fibrous histiocytoma, a rare tumor arising from the kidney.METHODS The clinical and pathological data from 4 cases of malignant fibrous histiocytoma of the kidney detected in our hospital are described.One case of special interest involved a giant cell subtype, the first to be reported in the oncology literature. The clinicopathologic features and prognostic factors of this tumor were analysed and summarized after reviewing 55 documented cases in the English and Chinese literature.RESULTS A palpable mass (71.2%), emaciation (54.2%) and pain (54,2%) were common manifestations in renal MFH, Of all the cases, 51 were identified as a storiform-pleomorphic subtype by pathologists. Inconsideration of all the prognosis related factors, the residual tumor and high TNM stage predicted a shortened survival duration, but the symptom of a fever served as a better prognostic factor.CONCLUSION Malignant fibrous histiocytoma which arises from the kidney is a rare pathologic type, and possesses a high tendency towards local recurrence and distant metastasis. Despite the poor prognosis, early detection and radical surgery can prolong survival in selected cases.