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Expression of multi-drug resistance genes (mdr1, mrp1, bcrp) in primary oral squamous cell carcinoma
R E Friedrich1, C Punke, A Reymann
1Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitaetsklinikum Hamburg-Eppendorf, Universitaet Hamburg, Germany. rfriedri@uke.uni-hamburg.de
Unlabelled:
The expression of resistance genes can cause the ineffectiveness of chemotherapeutics for the treatment of cancer. Therefore, known resistance genes were investigated in oral squamous cell carcinoma (OSCC) and the results were compared with clinico-pathological findings.
Materials And Methods:
Fresh frozen samples of 45 primary OSCC were investigated for the expression of mdr1 (p-glycoprotein-mediated multi-drug resistance), mrp1 (multi-drug resistance-related protein) and bcrp (breast cancer-related protein), using a reverse transcriptase PCR. The gene products were revealed immunohistochemically on representative slices of the same tumor sample. The results were compared with TNM stage grouping [SG, (UICC, 1987)], HPV infection and p53 mutations (exons 5-8).
Results:
The expression of the resistance genes was independent of age, sex, localisation of the tumor, HPV infection and p53 mutations. SG did not correlate to mdr1 and mrp1. On the other hand, bcrp expression increased 2.7-fold between SG III and IV OSCC. Loss of differentiation was associated with an increased expression of mdr1 (p=0.06), mrp1 (p<0.01) and bcrp (p<0.01). The bcrp expression correlated with shorter survival periods. Expression of mrp1 and mdr1 did not correlate positively in a linear pattern. Expression of mdr1 and bcrp moderately positively correlated (p<0.01).
Discussion:
Multi-drug resistance genes can be up-regulated in OSCC. The expression of at least one of these genes is up-regulated in SG-IV OSCC. Determining these genes could probably support current studies on therapeutic effects in OSCC, e.g. new cytostatic drugs.
Insights
Resistance genes like mdr1, mrp1, and bcrp can be upregulated in oral squamous cell carcinoma (OSCC), impacting chemotherapy effectiveness. BCRP expression correlates with advanced stages and poorer survival in OSCC patients.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Chemotherapeutic resistance in cancer is often mediated by the expression of specific genes.
- Oral squamous cell carcinoma (OSCC) poses a significant challenge in cancer treatment due to potential treatment ineffectiveness.
Purpose of the Study:
- To investigate the expression of known drug resistance genes in OSCC.
- To correlate the expression of these genes with clinico-pathological findings and patient outcomes.
Main Methods:
- Expression analysis of mdr1, mrp1, and bcrp genes using reverse transcriptase PCR in 45 primary OSCC samples.
- Immunohistochemical validation of gene products.
- Correlation with TNM stage, HPV infection, and p53 mutations.
Main Results:
- Gene expression was independent of age, sex, tumor site, HPV, and p53 mutations.
- BCRP expression showed a 2.7-fold increase in Stage IV OSCC compared to Stage III.
- Increased expression of mdr1, mrp1, and BCRP was associated with loss of differentiation and shorter survival periods.
Conclusions:
- Multi-drug resistance genes are frequently upregulated in OSCC, particularly in advanced stages (Stage IV).
- Determining the expression of these resistance genes may aid in developing targeted therapies and improving treatment strategies for OSCC.
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