Multidrug resistance gene and P-glycoprotein expression in anaplastic carcinoma of the thyroid.

Abstract

The resistance of malignant tumors to chemotherapy with anticancer drugs has been considered to be due partly to overexpression of the multidrug resistance gene (mdr1) and its gene product, P-glycoprotein (P-GP), which acts as a drug efflux pump for several chemotherapeutic agents. In order to elucidate the mechanism of anticancer drug resistance in anaplastic thyroid carcinoma with very poor prognosis, we examined the expression of mdr1 mRNA and P-GP, and analyzed their relationships to chemotherapy response. Twenty surgical samples from 16 patients with anaplastic thyroid carcinoma were used. The mdr1 mRNA expression was examined by reverse transcription and polymerase chain reaction, and P-GP expression was evaluated by an immunohistochemical method using JSB-1 monoclonal antibody. Of the 20 clinical samples, expression of mdr1 mRNA and P-GP was observed in three and four samples, respectively. Three of the patients from whom the samples were obtained had been given anticancer drugs before biopsy. Of 12 patients who received chemotherapy for clinically evaluable diseases, 2 responded well, but 10 showed no response. All except one patient died of cancer progression. There was no relationship between the response to chemotherapy and the expression of mdr1 and P-GP. The expression of mdr1 mRNA and/or P-GP was observed in 5 of 16 patients with anaplastic thyroid carcinoma. However, the appearance of anticancer drug resistance in anaplastic thyroid carcinoma may not be explained solely by the expression of mdr1 and P-GP.