Expression of Multi-drug Resistance Genes (mdr1, mrp1, bcrp) in Primary Oral Squamous Cell Carcinoma

Abstract

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.