2ND PRIMARY HEAD AND NECK SQUAMOUS-CELL CARCINOMA PREDICTED BY THE GLUTATHIONE-S-TRANSFERASE EXPRESSION IN HEALTHY TISSUE IN THE DIRECT VICINITY OF THE FIRST TUMOR

BACKGROUND: Glutathione S-transferases (GST) are known to play a role in the detoxification of carcinogens. Individual isoenzymes of the alp ha-, mu-, and pi-class vary in substrate specificities, tissue distrib ution, and activities among individuals. GST-pi expression has been sh own to be increased in preneoplastic and neoplastic lesions. GST-mu is known to play a role in detoxification of epoxides released from ciga rette smoke, and individuals with low GST-mu activity have a relativel y high risk to develop smoking-related lung and laryngeal cancer. The occurrence of a second primary tumor (SPT) in the whole respiratory an d upper aerodigestive tract is an important factor for mortality in he ad and neck squamous cell. carcinoma (HNSCC), and, at present, there a re no markers that are available to predict which patient has increase d chances of developing an SPT. Risk-assessment by use of biomarkers, particularly the ones that can be obtained with noninvasive techniques , are of great value in predicting prognosis and hence possibly more a ggressive treatment and follow-up in selected patient groups. EXPERIME NTAL DESIGN: In a nested case control study, 20 patients who had previ ous history of oral cancer were used; 10 of the 20 had developed an SP T, and the other 10 patients were minimally 7 years free of disease. T he expression of GST-pi, GST-mu, and GST-alpha was immunohistochemical ly analyzed using apparently normal oral mucosa, free of tumor or dysp lasia, obtained from the resection edges around the primary tumor. In another experiment, the three GST isoenzymes were immunohistochemicall y analyzed using exfoliated cells, obtained noninvasively hom several sites of the upper aerodigestive tract of the apparently normal-lookin g mucosa of HNSCC patients (n = 25) and of control individuals (n = 10 ). RESULTS: The expression of all GST was significantly higher (p < 0. 001) in the suprabasal and superficial layers of the mucosa at risk. A lso, in cell scrapes of clinically healthy mucosa of HNSCC patients, w e observed a significantly higher expression (p < 0.001) of GST-pi and GST-mu compared with their matched controls. For GST-alpha, we observ ed a more heterogenous expression pattern in these exfoliated cells. C ONCLUSIONS: Expression of GST-pi, -mu, and -alpha in normal tissue in the direct vicinity of the first tumor seems to have predictive value for the development of an SPT.