THE ENDA ENDOMETRIAL ADENOCARCINOMA - AN ESTROGEN-SENSITIVE, METASTASIZING, INVIVO TUMOR-MODEL OF THE RAT

A high percentage of endometrial carcinomas contain oestrogen and prog esterone receptors. For endocrine therapy of recurrent endometrial car cinoma, only high-dose progestins are in clinical use. As, therefore, the development of new endocrine treatment strategies is of great inte rest, suitable animal models for this tumour are essential. Up to now, only human tumour xenografts transplanted in immune-deficient nude mi ce, but no syngeneic in vivo tumour models, have been available. In th e present article we describe the hormone sensitivity of the EnDA endo metrial adenocarcinoma of the DA/Han rat growing as s.c. implants in D A/Han rats and athymic nude mice in serial passage. In both species, t he tumour expresses oestrogen, but no progesterone receptors. Transpla nted in DA/Han rats or nude mice, ovariectomy reduced tumour weight by 64% and 46% respectively. In both species substitution of ovariectomi zed animals with oestradiol restored tumour weights to intact control levels. Oestradiol substitution of intact animals did not further enha nce tumour growth. The growth of the primary tumour was inhibited by m edroxyprogesterone acetate (MPA) at a dose of 100 mg/kg by 67% and by tamoxifen at a dose of 20 mg/kg by 38%. Lung metastases were regularly seen in both species, although to a lesser extent in nude mice than i n DA/Han rats. Tamoxifen treatment did not alter the number of lung me tastases, whereas MPA or ovariectomy produced a significant reduction in the number of lung metastases. The EnDA endometrial carcinoma of th e DA/Han rat with respect to its oestrogen sensitivity, oestrogen rece ptor expression, morphology and metastatic growth, grossly resembles a typical endometrial adenocarcinoma and can therefore be regarded as a useful in vivo experimental model for the evaluation of new endocrine treatment strategies.