Immunohistochemical evaluation of uteri from female rhesus monkeys (macaca mulatta) after cyclic intramuscular estrogen treatment

Abstract

OBJECTIVE: We previously reported significant changes of estrogen receptor-α (ER) and progesterone receptor (PR) in the uteri of perimenopausal female rhesus monkeys that underwent ovariectomies (OVXs) and were then randomized to receive intramuscular 17-estradiol treatment (E). We now report the expression of oncogenic receptors HER2 and BCL2.DESIGN: A prospective, randomized double-blind study.MATERIALS AND METHODS: Monkeys underwent OVXs and were randomly assigned to age-matched OVX plus E or OVX plus placebo vehicle (V) treatment groups. After a post-OVX interval of 30 ± 1.7 weeks (mean ± SEM), 15 monkeys received E (100 g/ml) and 13 monkeys received V every 3 weeks for 2 to 3 years. Paraffin sections of the uterine corpus and lower uterine segment (LUS) were stained using standard techniques for HER2 and BCL2. Immunohistochemical evaluation of glandular (G), myometrium (M), and stromal (S) compartments were performed separately on uterine corpus and LUS regions. Scoring for HER2 and BCL2 were performed by multiplying the percentage of positive cells (0-25% =1, 26-50% =2, 51-75% =3, and 76-100% = 4) by the intensity of staining (graded 1-4). Mixed model analysis was used to account for correlation between repeated measures made within a given monkey.TableGroupNMeanMedianNMeanMedianWilcoxon P-valueHER2 Corpus G150.200131.5400.112HER2 Corpus M150.000130.000NAHER2 Corpus S150.000130.000NAHER2 LUS G150.200130.6900.235HER2 LUS M150.000130.000NAHER2 LUS S150.000130.000NABCL2 Corpus G152.671101.5000.218BCL2 Corpus M154.604122.6710.251BCL2 Corpus S152.201121.330.50.440BCL2 LUS G152.332102.700.50.597BCL2 LUS M154.003123.924.50.980BCL2 LUS S151.460121.5800.546 Open table in a new tab CONCLUSIONS: Although E administration in ovariectomized monkeys results in a decrease in ER and an increase in PR in the uterus, we now demonstrate that E administration does not significantly change the expression of HER2 and BCL2. OBJECTIVE: We previously reported significant changes of estrogen receptor-α (ER) and progesterone receptor (PR) in the uteri of perimenopausal female rhesus monkeys that underwent ovariectomies (OVXs) and were then randomized to receive intramuscular 17-estradiol treatment (E). We now report the expression of oncogenic receptors HER2 and BCL2. DESIGN: A prospective, randomized double-blind study. MATERIALS AND METHODS: Monkeys underwent OVXs and were randomly assigned to age-matched OVX plus E or OVX plus placebo vehicle (V) treatment groups. After a post-OVX interval of 30 ± 1.7 weeks (mean ± SEM), 15 monkeys received E (100 g/ml) and 13 monkeys received V every 3 weeks for 2 to 3 years. Paraffin sections of the uterine corpus and lower uterine segment (LUS) were stained using standard techniques for HER2 and BCL2. Immunohistochemical evaluation of glandular (G), myometrium (M), and stromal (S) compartments were performed separately on uterine corpus and LUS regions. Scoring for HER2 and BCL2 were performed by multiplying the percentage of positive cells (0-25% =1, 26-50% =2, 51-75% =3, and 76-100% = 4) by the intensity of staining (graded 1-4). Mixed model analysis was used to account for correlation between repeated measures made within a given monkey. CONCLUSIONS: Although E administration in ovariectomized monkeys results in a decrease in ER and an increase in PR in the uterus, we now demonstrate that E administration does not significantly change the expression of HER2 and BCL2.