Steroid hormone receptors in normal and malignant human renal tissue: relationship with progestin therapy

Abstract

Documented hormone dependence of renal tumors in animal models, hypothetical hormonal environment of human kidney neoplasms and their controversial response to endocrine therapy prompted us to undertake a prospective multicentric cooperative study to evaluate the hormone-dependence/responsiveness of renal tumors. Patients with renal carcinoma were stratified according to the TNM classification and after nephrectomy were treated with high-dose medroxyprogesterone acetate (MPA). Specimens of tumor and healthy surrounding kidney tissue were studied for titration of steroid receptor proteins (78 for androgen, AR, 89 for estrogen, ER, and progestin, PgR). Their true receptor nature was estimated. Very low titers (on an average less than 10 fmol/mg protein) were found, especially for ER and PgR in neoplastic samples. Occurrence rate of AR was low for both tissues (less than 20%), whereas ER and PgR were detected at a higher frequency in healthy parenchyma than in tumor tissue (42.2 vs 23.3% and 30.7 vs 11.2%, respectively). AR was moderately affected by metastatic status of the disease and by sex. All three steroid receptors were simultaneously detected in normal tissue in 11.7% of cases and in tumor tissue in only 3.8%. No significant correlation between receptor status in the tumor and clinical response to hormone therapy was found. In 27 cases who received adjuvant MPA therapy, relapses were respectively 43.8 and 18.2% in the patients with negative receptors or with at least one detectable receptor. In metastatic renal carcinoma, stabilization of the disease with MPA was achieved more frequently in receptor-negative patients. Therefore, we conclude that the receptor assay is not a valid tool to select renal carcinoma patients for therapy with MPA.