Expression of P-glycoprotein, a multidrug-resistance gene product, is induced by radiotherapy in patients with oral squamous cell carcinoma

Abstract

BACKGROUND. It has been observed that patients who have previously undergone radiotherapy have a lower rate of response to chemotherapy. METHODS. The authors investigated the effects of radiation on the expression of P-glycoprotein (Pgp), a multidrug-resistance gene product, in 56 patients with primary oral cancer. No patients received prior or concurrent chemotherapy. The 56 patients consisted of 3 groups: 1) 20 patients with preradiation or pretreatment specimens only, 2) 18 patients with both pre- and postradiation specimens, and 3) 18 patients with postradiation specimens only. Pgp expression was determined by immunohistochemistry with two monoclonal antibodies, C219 and C494. RESULTS. Among patients in Groups 1 and 2, only 1 (2.6%) and 2 (5.3%) patients had Pgp expression in their tumors before treatment with C219 and C494, respectively. For Group 2 patients, 66.7% and 72.2% had tumors that expressed Pgp with the two antibodies, respectively, only after and not prior to radiation. When patients in Groups 2 and 3 were combined, 63.9% and 72.2% had Pgp expression with the two antibodies, respectively, after radiation. Pgp expression was significantly induced after radiation compared with expression before treatment (P < 0.001). Overexpression of p53 protein, detected by immunohistochemistry with DO-7 antibody, was seen in the tumors of 40 patients (71.4%), and the status was quite consistent throughout radiotherapy. Pgp expression had no significant association with p53 protein expression. CONCLUSIONS. Pgp expression was significantly induced by radiation in human oral cancers. This induction of Pgp expression likely confers multidrug resistance to the cancer cells and may affect the efficacy of subsequent or concurrent chemotherapy. It may explain the lower rate of response to chemotherapy among patients who have previously had radiotherapy.link_to_subscribed_fulltex