Expression of multi-drug resistance genes (mdr1, mrp1, bcrp) in primary oral squamous cell carcinoma.
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.


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).


CONCLUSIONS
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.
Friedrich
R E
RE
Klinik für Mund-, Kiefer- und Gesichtschirurgie, Universitaetsklinikum Hamburg-Eppendorf, Universitaet Hamburg, Germany. rfriedri@uke.uni-hamburg.de
Punke
C
C
Reymann
A
A
D018435:ATP Binding Cassette Transporter, Subfamily B / Q000235:genetics* / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002294:Carcinoma, Squamous Cell / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D019450:Genes, MDR / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D018435:ATP Binding Cassette Transporter, Subfamily B; D012334:RNA, Neoplasm