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Multidrug resistance gene and P-glycoprotein expression in anaplastic carcinoma of the thyroid
T Yamashita1, M Watanabe, M Onodera
1Ito Hospital, Tokyo, Japan.
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.
Insights
Multidrug resistance gene (mdr1) and P-glycoprotein (P-GP) are often linked to chemotherapy resistance. This study found no direct relationship between mdr1/P-GP expression and chemotherapy response in anaplastic thyroid carcinoma.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Anaplastic thyroid carcinoma (ATC) exhibits a very poor prognosis, often linked to resistance to chemotherapy.
- Multidrug resistance (MDR) mediated by the multidrug resistance gene (mdr1) and its product, P-glycoprotein (P-GP), is a known mechanism of anticancer drug resistance.
Purpose of the Study:
- To investigate the expression of mdr1 mRNA and P-GP in ATC.
- To analyze the relationship between mdr1/P-GP expression and the response to chemotherapy in ATC patients.
Main Methods:
- Analysis of 20 surgical samples from 16 ATC patients.
- Reverse transcription and polymerase chain reaction (RT-PCR) for mdr1 mRNA expression.
- Immunohistochemical evaluation of P-GP expression using the JSB-1 monoclonal antibody.
Main Results:
- mdr1 mRNA and P-GP expression were detected in a subset of ATC samples (3/20 and 4/20, respectively).
- Chemotherapy response was poor in most patients (2/12 responded well, 10/12 showed no response).
- No significant correlation was found between mdr1/P-GP expression levels and chemotherapy response or patient survival.
Conclusions:
- The expression of mdr1 and P-GP alone does not fully explain the observed anticancer drug resistance in anaplastic thyroid carcinoma.
- Other mechanisms likely contribute to the limited efficacy of chemotherapy in ATC.