Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with raloxifene.

OBJECTIVE: To evaluate Ki-67 antigen expression in the mammary epithelium of female rats in persistent estrus treated with raloxifene. MATERIALS AND METHODS: Forty-one Wistar-Hannover rats in persistent estrus induced by 1.25 mg of testosterone propionate were randomly divided into two groups: Group A (control, n = 21) in which the animals received only the vehicle (propylene glycol) and Group B (experimental, n = 20) in which the rats received 750 µg/day of raloxifene by gavage. After 21 days of treatment, all the animals were sacrificed and the first pair of abdominal-inguinal mammary glands was extirpated and fixed in 10% buffered formalin to investigate Ki-67 expression by immunohistochemistry. The data were analysed using Student's t-test (p < 0.05). RESULTS: The percentage of Ki-67-stained nuclei per 500 cells in the mammary epithelium was 42.33 ± 6.18 and 15.51 ± 3.71 [mean ± standard error of the mean (SEM)] in the control and experimental groups, respectively (p < 0.001). CONCLUSION: Raloxifene treatment significantly reduced Ki-67 expression in the mammary epithelium of rats in persistent estrus.

The relationship between estrogen receptor gene polymorphism and mammographic density in postmenopausal women.

OBJECTIVE: To assess the relationship between the presence of PVUII and XBAI polymorphisms in the estrogen receptor α gene and mammographic density in postmenopausal women. METHODS: For the present analysis, 189 postmenopausal women who had never used hormonal therapy and who did not have clinical or mammographic features were selected. Based on the ACR-BIRADS(®) 2003 classification, the mammographic density was determined by three independent readers (two subjective ratings and one computerized). Blood samples were available to extract DNA according to KIT GFX(®) protocol. PCR-RFLP was then used to identify the polymorphisms. RESULTS: There was a high degree of agreement among the three readers to determine the mammographic density (κ > 0.75). Sixty women (32%) had dense breasts and 129 (68%) had non-dense breasts. The PVUII polymorphism was found in 132 (69.8%) of 189 women, while the XBAI polymorphism was found in 135 (71.4%) women. Parity (p = 0.02) and body mass index (p < 0.0001) were associated with mammographic density. It was observed that, for the XBAI polymorphism, women with two mutated alleles were approximately 2.5 times more likely to be classified in the dense breasts group (p = 0.003) and the presence of both wild alleles was associated with fibroglandular tissue replacement by fat (p = 0.02). CONCLUSIONS: There was no significant association of the PVUII polymorphism in the estrogen receptor α gene with mammographic density (p = 0.34). However, the XBAI polymorphism was observed at a higher mutated homozygous frequency in women with dense breasts and there was an increased frequency of wild-type homozygous and heterozygous women with fat-replaced breasts (p = 0.01).

Analysis of human mammary fibroadenoma by Ki-67 index in the follicular and luteal phases of menstrual cycle.

OBJECTIVES: Fibroadenoma is the most common benign mammary condition among women aged 35 or younger. Expression of Ki-67 antigen has been used to compare proliferative activity of mammary fibroadenoma epithelium in the follicular and luteal phases of the menstrual cycle. MATERIALS AND METHODS: Ninety eumenorrheic women were selected for tumour excision; they were assigned to either of the two groups, according to their phase of menstrual cycle. At the end of the study, 75 patients with 87 masses were evaluated by epithelial cell Ki-67 expression, blind (no information given concerning group to which any lesion belonged). RESULTS: Both groups were found to be homogeneous relative to age, menarche, body mass index, previous gestation, parity, breastfeeding, number of fibroadenomas, family history of breast cancer and tabagism. Median tumour size was 2.0 cm and no relationship between proliferative activity and nodule diameter was observed. No typical pattern was observed in the expression of Ki-67 in distinct nodules of the same patient. Average values for expression of Ki-67 (per 1000 epithelial cells) in follicular and luteal phases were 27.88 and 37.88, respectively (P = 0.116). CONCLUSION: Our findings revealed that proliferative activities in the mammary fibroadenoma epithelium did not present a statistically significant difference in the follicular and luteal phases. The present study contributes to clarifying that fibroadenoma is a neoplasm and does not undergo any change in the proliferative activity during the menstrual cycle.