A PATIENT WITH ADRENOCORTICAL CARCINOMA - CHARACTERIZATION OF ITS BIOLOGICAL-ACTIVITY AND DRUG-RESISTANCE PROFILE

We describe a patient with a metastasized adrenocortical cancer who ex hibited excessive production of both glucocorticoids and mineralocorti coids combined with suppressed androgen production, Unusual steroid me tabolites found in the patient's urine have not been described previou sly in association with this tumor type, Investigation of the multidru g resistance phenotype in single-cell suspensions of the tumor reveale d low expression of multidrug resistance protein but high expression o f P-glycoprotein (Pgp) and lung resistance-related protein, Functional Pgp in these tumor cells was shown by the modulatory effect of PSC833 on daunorubicin accumulation. Mitotane, at a concentration achieved i n this patient's plasma, completely reversed the Pgp-related resistanc e both in the Pgp-overexpressing KB8-5 cell line and in the patient's tumor cells, On the basis of these in vitro results, the patient was t reated with a combination of multidrug resistance drugs (doxorubicin, vincristine, and etoposide) plus mitotane as a Pgp modulator, This tre atment was ineffective, however, A chemosensitivity assay demonstrated that the tumor cells were highly resistant to the drugs used, The adr enocortical cancer cells expressed mutant p53, and no evidence for ind uction of apoptosis by these drugs was found.