1994 Volume 7 Issue 3 Pages 379-385
The effects of prolonged treatment with ovarian steroid hormones on the development of endometrial adenocarcinoma were investigated in ICR mice. For the tumor induction, a mixed solution of ethylenethiourea (ETU, 100mg/kg body weight) and sodium nitrite (NaNO2, 70mg/kg body weight) was administered weekly to 60 mice by stomach tube for 26 weeks. Additional 40 animals received distilled water in the same manner. At 45 weeks of study, a silastic or polyethylene tube loaded with progesterone or 17β-estradiol was implanted in the dorsal subcutis of animals. The animals were killed at 52 weeks of study and subjected to pathological examinations including immunohistochemical staining for nuclear estrogen receptors on paraffin section. Prolonged treatment with progesterone for 8 weeks (45-52 weeks) suppressed the development of atypical hyperplasia slightly but not of adenocarcinoma. The incidences of these lesions were not affected by 17β-estradiol. Immunohistochemical staining for nuclear estrogen receptors denoted positive reaction in glandular cells of atypical hyperplasia but the intensity of staining was less than that in the normal endometrial gland. The nucleus in the endometrial adenocarcinoma was generally negative for the staining or showed heterogenous distribution of faintly positive reaction. These evidences indicate that effacement or functional impairment of nuclear steroid receptors are likely to be important in malignant transformation of the precursor lesions into adenocar-cinoma in the endometrium of mice.
