Evaluation of heparanase and matrix metalloproteinase-9 in patients with cutaneous malignant melanoma

• Published in: Journal of dermatology Vol. 39; no. 4; pp. 339 - 343
• Main Authors: CHEN, Yanhui, CHEN, Ying, HUANG, Liyong, YU, Jianbin
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Publishing Ltd 01.04.2012; Wiley Subscription Services, Inc
• Subjects: Adult; Aged; cutaneous malignant melanoma; Female; Glucuronidase - metabolism; heparanase; Humans; Immunohistochemistry; junctional nevus; Lymphatic Metastasis - physiopathology; Male; matrix metalloproteinase; Matrix Metalloproteinase 9 - metabolism; Melanoma; Melanoma - enzymology; Melanoma - pathology; Melanoma - secondary; Metastasis; Middle Aged; Nevus - enzymology; Nevus - pathology; Skin cancer; Skin Neoplasms - enzymology; Skin Neoplasms - pathology
• ISSN: 0385-2407; 1346-8138
• DOI: 10.1111/j.1346-8138.2011.01441.x

Elevated heparanase and matrix metalloproteinase (MMP)‐9, frequently found in human cancer, is a major cause of degradation of the extracellular matrix (ECM) and basement membrane (BM), thus facilitating tumor cell migration and invasion. Although a lot of work has been done, the role of heparanase and MMP‐9 has not been delineated in skin cancer progression. The purpose of this study was to do such an exploration. To investigate the role of heparanase and MMP‐9 in cutaneous malignant melanoma (CMM) development, we performed immunohistochemical analysis to detect the alternation of these two factors in paraffin‐embedded biopsy specimens of normal skin, junctional nevi and CMM. It is interesting to note that the expression profile of heparanase and MMP‐9 was similar. Contrary to negative staining in normal skin, overexpression of heparanase and cytoplasmic MMP‐9 was observed in as many as 70% of CMM, whereas only 10% of the junctional nevi exhibited faint staining (P = 0.0005, P = 0.0000). Considering the lymph node (LN) metastasis, the expression of the two factors is significantly higher in LN‐positive lesions than that in LN‐negative lesions (P = 0.0295, P = 0.0013). Meanwhile, there was positive correlation between the expression of MMP‐9 and heparanase (r = 0.689, P = 0.003). The first expression of MMP‐9 and heparanase occurs at benign lesions. However, the significantly increased expression in advanced CMM stages, particularly in LN‐positive metastasis lesions, might synergistically contribute to degradation of ECM and BM, therefore promoting carcinogenesis and metastasis.