Expression of the Multiple Drug Resistance Gene in Human Renal Cell Carcinoma Depends on Tumor Histology, Grade, and Stage

Levels of mRNA expressed by the multidrug resistance gene MDRl were examined in 23 renal cell carcinoma samples and adjacent normal kidney cortex using reverse-transcription PCR. Comparison of MDRl levels between histological types revealed that there was on average significantly more MDRl in clear cell tumors than in oncocytomas (0.89 ±0.10 versus 0.28 ± 0.20, ratio of MDRl in tumor cells to the drug-resistant cell line KB-8, P < 0.05). The mean MDRl level of all of the non-oncocytoma tumors was not significantly different from the mean MDRl level of normal adjacent kidney (0.89 ± 0.10 versus 1.11 ± 0.12, P = 0.07). However, the mean MDRl level of the more undifferentiated clear cell tumors was significantly lower than the mean MDRl level of adjacent normal kidney (0.74 ± 0.10 versus ± 0.12, P < 0.05). MDRl levels in early stage, clear cell tumors (/i = 14) were lower than in tumors that had spread into perinephric tissue or had metastasized (n = 6) (0.77 ± 0.08 versus 1.24 ± 0.30, P < 0.05). In conclusion, MDRl expression decreases in the more undifferentiated tumors, but still remains at levels high enough to be drug resistant. Higher MDRl expression in the invasive tumors compared with noninvasive tumors suggests that MDRl expression and invasiveness may be linked.