Asian Science Seminar             ASS-1


Preferential Expression of Heparanase Protein Correlates with Early Invasion and Progression of Oral Mucosal Melanoma


Rosario Santos Rivera1, 2, Hitoshi Nagatsuka2, Ryo Tamamura2, Jing Xiao2, 3 and Noriyuki Nagai2

1College of Dentistry, University of the East, Manila, Philippines

2Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama University, Japan

3Department of Oral Pathology, College of Stomatology, Dalian Medical University, China


Oral mucosal melanoma (OMM) is an aggressive tumor with frequent metastasis. Most OMMs begin with an in situ phase and then progressed to invasive phase. Heparanase is an endo-beta-D-glucuronidase, which cleaves heparan sulfate (HS) chains found in basement membrane (BM) and extra-cellular matrix (ECM). Heparanase released by invading neoplastic cells removes HS chains from the BM resulting to increased permeability. The expression of heparanase has been studied in various neoplasms and its expression has been related to invasion, progression, angiogenesis and metastasis. The objective of the study was to determine the immunohistochemical expression of heparanase in normal oral mucosa, oral melanosis, primary OMM and those that metastasized to the lymph nodes. Results revealed that the melanocytes in normal mucosa and in oral melanosis were negative to heparanase. However, melanoma cells in in situ, invasive and metastatic OMM were positive. A gradual increase in the expression was observed during the transformation from in situ to invasive phase and in the progression to early invasive phase. However, in deeper tumor areas, heparanase was limited to melanoma cells individually invading the ECM, near the vessels and at the invasive fronts. Several tumor cells that metastasized to the lymph nodes also expressed heparanase. In conclusion, heparanase was only expressed by melanoma cells and not by normal melanocytes. Heparanase expression was most intense during the transformation from in situ to invasive phase and in early invasive phase suggesting its correlation with the early invasion and progression of OMM.