Prediction of clinical outcome with estrogen and progestin receptor concentrations and their relationships to clinical and histopathological variables in endometrial cancer.

Concentrations of cytosol estrogen (ERC) and cytosol progestin (PRC) receptors were assayed in malignant tissue specimens of 230 patients with endometrial cancer, and those of nuclear estrogen and nuclear progestin receptors, and 17 beta-hydroxysteroid dehydrogenase activities in about 100 specimens. Endometrial cancer was at an early stage in 205 and advanced in 25 patients. As a supplement to surgical and radiation therapy, all patients received p.o. medroxyprogesterone acetate (100 mg a day) for 2 years. The follow-up time varied from 12 to 96 months (median, 42 months). Concentrations of ERC, PRC, nuclear estrogen, and nuclear progestin receptors in endometrial cancer tissue were significantly lower in clinical stages III-IV than in clinical stage I. In clinical stage I, ERC and PRC appeared in significantly lower concentrations in anaplastic than in moderately and well differentiated malignancies. The concentrations of these receptors were increased in obese patients, and the activity of 17 beta-hydroxysteroid dehydrogenase was increased in patients younger than 50 years, suggesting that endogenous female steroid hormones modify the pattern of female steroid receptors in malignant endometrium. In clinical stage I, 13 of 153 patients with adequate therapy contracted a recurrent disease. Poor prognosis was predicted by anaplastic structure of the malignancy (P less than 0.001), low tissue concentrations (0-30 fmol/mg protein) of ERC alone (P = 0.006), PRC alone (P = 0.010), and ERC and PRC simultaneously (P = 0.004). All 101 patients who simultaneously had ERC and PRC in concentrations higher than 30 fmol/mg protein remained disease free for 2 years, whereas all recurrences in patients with receptor-poor tumors appeared during the 2 years of medroxyprogesterone acetate treatment. In clinical stage II, with 30 patients, no prognosis indicators predicted the clinical outcome, whereas in clinical stages III + IV, with 25 patients, low ERC concentrations were associated with a worsened prognosis (P = 0.045). Conclusively, cytosol and nuclear estrogen and nuclear progestin receptor concentrations and 17 beta-hydroxysteroid dehydrogenase activity give valuable information about the endocrine associations in endometrial cancer. Cytosol estrogen and cytosol progestin receptors appeared to be useful predictors of recurrent disease. They also have the potential to distinguish between patients expected to benefit from adjuvant progestin therapy and those expected to be unresponsive to the same treatment.