PROGNOSTIC VALUE OF HEPARANASE EXPRESSION AND CELLULAR LOCALIZATION IN ORAL CANCER

Background. Metastases formation depends on the ability of tumor cells to invade basement membranes in a process involving enzymes capable of degrading extracellular matrix components. Methods. We examined the expression of heparanase in oral carcinomas and correlated its staining extent, intensity, and cellular localization with patients' outcome. Results. Quantitative real-time polymerase chain reaction (PCR) revealed over 4-fold increase in heparanase levels in oral carcinomas compared to adjacent normal tissue. Normal oral epithelium was found negative for heparanase, while all oral carcinomas stained positively for heparanase. Heparanase staining was associated with Ki67 staining, a measure of cell proliferation. Notably, whereas cytoplasmic localization of heparanase was associated with high-grade carcinomas, nuclear localization of the enzyme was found primarily in low-grade, well-differentiated tumors, and in all oral verrucous carcinomas. Conclusion. Expression level and cellular localization of heparanase could serve as an important diagnostic marker in patients with oral cancer. (C) 2010 Wiley Periodicals, Inc. Head Neck 33: 871-877, 2011