ABSTRACT
MULTIDRUG RESISTANCE IN LOCALLY ADVANCED BREAST CANCER
ATALAY, Mustafa Can
Ph. D., Department of Biotechnology
Supervisor: Prof. Dr. Ufuk GÜ / NDÜ / Z
June 2004, 70 pages
Breast cancer is the most frequently detected cancer among women. Early diagnosis leads to long term survival when the patients are treated with surgery, radiotherapy, chemotherapy, and hormone therapy. Unfortunately, advanced disease could still be encountered in some patients resulting in a poorer prognosis. The primary treatment modality is chemotherapy for this group of patients. Drug resistance is a serious problem resulting in the use of different drugs during chemotherapy and knowing the possibility of resistance before initiating first line chemotherapy may save time and money, and most importantly, may increase patient&rsquo / s survival. Therefore in this study, multidrug resistance is studied in locally advanced breast cancer patients. The breast tissues obtained from 25 patients both before and after chemotherapy were examined for drug resistance. Reverse transcriptase polymerase chain reaction was used for the detection of mdr1 and mrp1 gene expression. In addition, immunohistochemistry technique was used for P-glycoprotein and MRP1 detection. JSB-1 and QCRL-1 monoclonal antibodies were utilized to detect P-glycoprotein and MRP1, respectively.
Five patients were unresponsive to chemotherapy. In four of these patients mdr1 gene expression was induced by chemotherapy where as the fifth patient initially had mdr1 gene expression. In addition, Pgp positivity was detected in 9 patients after chemotherapy. Both the induction of mdr1 gene expression (p< / 0.001) and Pgp positivity (p< / 0.001) during chemotherapy were significantly related with clinical response.
On the other hand, mrp1 gene expression and MRP1 positivity were detected in 68% of the patients before the therapy. After chemotherapy, mrp1 expression increased to 84%. Although 80% of the clinically unresponsive patients had mrp1 gene expression, the relation between mrp1 expression and clinical drug response was not strong.
Thus, it can be concluded that in locally advanced breast cancer mdr1 gene expression during chemotherapy contributed to clinical unresponsiveness. However, mrp1 gene expression did not correlate strongly with the clinical response.
When RT-PCR and immunohistochemistry methods are compared in terms of detection of drug resistance, it seems that both methods gave similar and reliable results.
| Identifer | oai:union.ndltd.org:METU/oai:etd.lib.metu.edu.tr:http://etd.lib.metu.edu.tr/upload/12604991/index.pdf |
| Date | 01 June 2004 |
| Creators | Atalay, Mustafa Can |
| Contributors | Gunduz, Ufuk |
| Publisher | METU |
| Source Sets | Middle East Technical Univ. |
| Language | English |
| Detected Language | English |
| Type | Ph.D. Thesis |
| Format | text/pdf |
| Rights | To liberate the content for public access |
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