| Malignant melanoma (MM) is a high grade malignancy and often affects skin, then it is called cutaneous malignant melanoma (CMM). It was the third place (6.8%～20%) of all cutaneous malignant tumor. Though the incidence rate of our country is low, it is late for the patients to examine because of high death rate, year after year increasing incidence tendency and poor cognizance of CMM. Immunohistochemistry is the main method of clinical diagnosis when the tissue structure of some CMM is complex.Junctional nevus is pigmented nevus. Junctional nevus is labilization and is easy to cancerat, and the mechanisms is still unclear.Heparan sulfate (HS) is a biological macromolecules of entracellular matrix (ECM) and cell surface. It is a main element of basement membrane (BM). Heparanase is a kind of endoglycosidase. It can degrade the glycosidic bond between the side-line of heparan sulfate and core protein and damage the EC and BM directly. The studies have indicated that the heparanase is mainly distributed in the immuological tissues and cells. Such as placenta, spleen, lymph nodes, thymus, bore marrow and the activated T, B cells. It has a fundamental physiological function in the process of the period of the embryo growth, the cure of wound, tissue restore and the inflammation process. In the course of the tumor formation and development the tumor cells 'hijack' the physiological function of the above cells effectively. Perhaps releasing the heparanase' sulfate from the activated platelet as the vessel were in inflammation reaction, furthmore, making the inflammatory cells exude and stimulating vascular endothelial cellular split, in this way, the heparanase could induce the invasion, metastasis and the new vessel growth of tumor.Matrix Metalloproteinase 9 is one of the most important metastasis factors in vivo. It belongs to the gelatinases of the matrix metalloproteinase hyperfamily. Its main function is to decompose extracellularm matrix and participate in many physiological and pathological processes. Many kind of cells including the osteoclasts can express matrix metalloproteinase 9 and its expression is adjusted by many factors, for example: cell growth factor, hormone, TIMPs etc. Its main operational project is IV,V,VII,X collangen, gelatin and elastic fibers.Vascular endothelial growth factor C (VEGF-C) is astimulate factors and could induce the peri-tumoral lymphamgiogenesis.Comparing with skin and junctional nevus of benign lesion melanocyte system, further research on the mechanism of CMM and understanding the biologic feature of CMM in order to guide to clinical treatmeat is the most important project. This paper focuses on the biologic feature of CMM in order to explore the mechanism of CMM.Materials and MethodsThis experiment used paraffin specimen of CMM. Junctional nevus and normal skin of the first affiliated hospital of zhengzhou university from January, 1999 to June, 2005, including 30 cases of CMM, 30 cases of junctional nevus, 15 cases of normal skin. All above were diagnosed by more than two patho-associate professors of the department of pathology in the first affiliated hospital of Zhengzhou university. Using the immunohistochemistry, the relationship between Hpa, VEGF-C and MMP-9 in CMM, junctional nevus and normal skin has been studied.Statistical analysis: SPSS 10.0. Positive rate has been calculated by numetationdata; measurement data is expressed by X|-±S; using simple-sample Kolmogrov- Smirnov Analysis; Chi-square Analysis of numeration data is used to compare positive rate; Analysis of Variance is used to compare mean among three groups; Pearson Analysis is used to analyze the correlation of measurement data.α=0.05.Results1. Expression of the Hpa1.1 Comparison of positive rate of HpaIn CMM,junctional nevus and normal skin , the positive expression of Hpa is 63.3% (19 cases/30 cases), 6.6% (2 cases/ 30 cases) and 0 repectively. There is a significant difference of positivity of the expression of Hpa between CMM and junctional nevus (x~2=21.172, P=0.000, P<0.01). There is a significant difference of positivity of the expression of Hpa between CMM and normal skin (x~2=15.833, P=0.000, P<0.01). There is no significant difference of positivity of the expression of Hpa between junctional nevus and normal skin (x~2=1.66, P=0.196, P>0.05).1.2 Comparison of Expression Intensity of HpaThe intensity of expression of Hpa is 5.147±2.117, 2.812±1.210 respectively in CMM and junctional nevus. There is a significant difference of positivity of expression of Hpa between CMM and junctional nevus (P=0.000, P<0.01).2. Expression of the VEGF-C2.1 Comparison of positive rate of VEGF-CIn CMM,junctional nevus and normal skin , the positive expression of VEGF-C is 60% (18 cases/30 cases), 3.3% (1cases/ 30 cases) and 0 respectively. There is a significant difference of positivity of the expression of VEGF-C between CMM and junctional nevus (x~2=22.25, P=0.000, P<0.01); there is a significant difference of positivity of the expression of VEGF-C between CMM and normal skin (x~2= 15.000, P= 0.000, P<0.01); there is no significant difference of positivity of the expression of VEGF-C between junctional nevus and normal skin (x~2=0.833, P=0.361,P>0.05).2.2 Comparison of Expression Intensity of VEGF-CThe intensity of expression of VEGF-C is 5.326±2.067 and 3.142±1.011 respectively in CMM and junctional nevus. There is a significant difference of the expression of VEGF-C between CMM and junctional nevus (P=0.000, P<0.01); 3. Expression of the MMP-93.1 Comparison of positive rate of MMP-9In CMM,junctional nevus and normal skin , the expression of MMP-9 is 73.3% (22 cases/30 cases), 10% (3 cases/ 30 cases) and 0 respectively. There is a significant difference of the expression of MMP-9 between CMM and junctional nevus (x~2=32.089, P=0.000, P<0.01); there is a significant difference of the expression of MMP-9 between CMM and normal skin (x~2=18.333, P= 0.000, P<0.01); there is no significant difference of the expression of MMP-9 between junctional nevus and normal skin (x~2=2.500, P=0.114, P>0.05).3.2 Comparison of Expression Intensity of MMP-9The intensity of expression of MMP-9 is 5.632±2.625, 3.738±1.012 respectively in CMM and junctional nevus. There is a significant difference of expression of MMP-9 between CMM and junctional nevus (P=0.000, P<0.01).4. Correlation between Hpa,MMP-9 and VEGF-C in CMM4.1 Correlation between Hpa and VEGF-C in CMMIn the CMM tissue, the positive expression of Hpa is 63.3% (19 cases/30 cases) and the intensity is 5.147±2.117; the positive expression of VEGF-C is 60% (18 cases/30 cases) and the intensity is 5.326±2.067. Using Bivariate Correlations (Pearson) analysis, the significant correlation has been observed between the expression of Hpa and VEGF-C (r=0.726, P=0.001).4.2 Correlation between Hpa and MMP-9 in CMMIn the CMM tissue, the positive expression and the intensity of Hpa is 63.3% (19 cases/30 cases) and 5.147±2.117 respectively. The positive expression and the intensity of MMP-9 is 73.3% (22 cases/30 cases), and 5.632±2.625 respectively. Using Bivariate Correlations (Pearson) analysis, the expression of Hpa and MMP-9 showes significant correlations (r=0.689, .P=0.003).4.3 Correlation between MMP-9 and VEGF-C in CMMIn the CMM tissue, the positive expression and the intensity of MMP-9 is 73.3% (22 cases/30 cases), 5.632±2.625 respectively. The positive expression of VEGF-C is 60% (18 cases/30 cases) and the intensity of expression is 5.326±2.067. Using Bivariate Correlations (Pearson) analysis, there is significant correlation betweenMMP-9 and VEGF-C (r=0.736, P=0.001).5. The role of Hpa, VEGF-C and MMP-9 in CMM invasion and metastasis5.1 The role of Hpa in CMM invasion and metastasisThe difference of the expression of Hpa has been observed between the group of melanoma with lymphaden metastasis and the group of melanoma without lymphaden metastasis (P<0.05). There is a difference of the expression of Hpa between invasion melanoma I～III and invasion melanomaIV～V(P<0.05).5.2 The relationship between MMP-9 CMM invasion and metastasisThere is a difference of the expression of MMP-9 between melanoma with lymphaden metastasis and melanoma without lymphaden metastasis (P<0.05). There is a difference of the expression of MMP-9 between invasion melanoma I～III and invasion melanomaIV～V (P<0.05).5.3 The role of VEGF-C in CMM invasion and metastasisThere is a difference of the expression of VEGF-C between melanoma with lymphaden metastasis and melanoma without lymphaden metastasis (P<0.05). There is a difference of the expression of VEGF-C between invasion melanoma I ~ III and invasion melanomaIV～V (P<0.05).Conclusions:1. The expression of Hpa, VEGF-C and MMP-9 has been up-regulated in CMM than those in junctional nevus and normal skin. The study might suggest that the over expression of Hpa, VEGF-C and MMP-9 might participate the occurrence and development of CMM.2. The expression of Hpa and VEGF-C in CMM has shown significant correlation. The two might play pivotal roles together in the process of CMM invation.3. The expression of Hpa and MMP-9 in CMM is significant correlation. The two factors might promote CMM invation together.4. The expression of MMP-9 and VEGF-C in CMM is significant correlation. The three facors might play equal roles and might rely on each other in the process of CMM invation. 5. The expression of Hpa, MMP-9 and VEGF-C has been up-regulated in melanoma with lymphaden metastasis than those in melanoma without lymphaden metastasis. The over-expression has also been observed in invasion melanoma IV～V than those in invasion melanoma I～III. The results might suggest that the excessive expression of Hpa,MMP-9 and VEGF-C might be highly related to the invasion and metastasis of CMM. |
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