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Breast Cancer Research
Published in: Breast Cancer Research 3/2005

Open Access 01-06-2005 | Research article

Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle

Authors: Maria Alicia H Navarrete, Carolina M Maier, Roberto Falzoni, Luiz Gerk de Azevedo Quadros, Geraldo R Lima, Edmund C Baracat, Afonso CP Nazário

Published in: Breast Cancer Research | Issue 3/2005

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Abstract

Introduction

During the menstrual cycle, the mammary gland goes through sequential waves of proliferation and apoptosis. In mammary epithelial cells, hormonal and non-hormonal factors regulate apoptosis. To determine the cyclical effects of gonadal steroids on breast homeostasis, we evaluated the apoptotic index (AI) determined by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) staining in human mammary epithelial cells during the spontaneous menstrual cycle and correlated it with cellular proliferation as determined by the expression of Ki-67 during the same period.

Methods

Normal breast tissue samples were obtained from 42 randomly selected patients in the proliferative (n = 21) and luteal (n = 21) phases. Menstrual cycle phase characterization was based on the date of the last and subsequent menses, and on progesterone serum levels obtained at the time of biopsy.

Results

The proliferation index (PI), defined as the number of Ki-67-positive nuclei per 1,000 epithelial cells, was significantly larger in the luteal phase (30.46) than in the follicular phase (13.45; P = 0.0033). The AI was defined as the number of TUNEL-positive cells per 1,000 epithelial cells. The average AI values in both phases of the menstrual cycle were not statistically significant (P = 0.21). However, the cell renewal index (CRI = PI/AI) was significantly higher in the luteal phase (P = 0.033). A significant cyclical variation of PI, AI and CRI was observed. PI and AI peaks occurred on about the 24th day of the menstrual cycle, whereas the CRI reached higher values on the 28th day.

Conclusions

We conclude that proliferative activity is dependent mainly on hormonal fluctuations, whereas apoptotic activity is probably regulated by hormonal and non-hormonal factors.
Appendix
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Metadata
Title
Assessment of the proliferative, apoptotic and cellular renovation indices of the human mammary epithelium during the follicular and luteal phases of the menstrual cycle
Authors
Maria Alicia H Navarrete
Carolina M Maier
Roberto Falzoni
Luiz Gerk de Azevedo Quadros
Geraldo R Lima
Edmund C Baracat
Afonso CP Nazário
Publication date
01-06-2005
Publisher
BioMed Central
Published in
Breast Cancer Research / Issue 3/2005
Electronic ISSN: 1465-542X
DOI
https://doi.org/10.1186/bcr994

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