Glutathione-S-transferase expression in oral squamous cell carcinoma

BACKGROUND: A large number of oral cancer patients shows poor or partial response to chemotherapy and the mechanisms are poorly understood. Glutathione-S-transferase (GST) is one of the molecules involved in resistance to natural product-based chemotherapeutics. It is an enzyme able to conjugate several substances (metabolites, drugs) to reduct glutathione. Today several isoenzymes of GST are known: GST-alpha, GST-mu, GST-pi, GST-theta. Over-expression of glutathione S-transferase-pi class isozyme is often associated with malignant transformation. Several studies reported that GST-pi staining patterns and their distribution may be helpful in identifying high-risk oral lesions. However, GST is surely involved in resistance to alchilant agents. OBJECTIVE: To verify the possibility of implication of GST in oral cancerogenesis and in natural chemioresistance, the authors examined the protein expression patterns by immunohistochemistry in paraffin-embedded specimens of primary untreated oral cancers (OSCC). METHODS: GST-a and GST-pi expression in 17 cases of OSCC at different degree of cellular differentiation have been evaluated by immunohistochemistry. RESULTS: The GST-pi expression in primary tumours predominantly varied from mild to moderate levels. The GST-a expression was often quite similar to GST-pi expression with a few exceptions. CONCLUSIONS: Expression of GST enzymes is an important signal for multidrug resistance: positive staining for both GST-pi and GST-a could constitute a hallmark of chemoresistant groups of OSSC