Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer

Abstract

Estrogen receptor (ER) is essential for estrogen-dependent growth, and its level of expression is considered a crucial determinant of response to endocrine therapy and prognosis in ER-positive breast cancer. On the other hand, the clinical role of progesterone receptor (PgR) in ER-positive breast cancer remains controversial, although testing of PgR by immunohistochemistry (IHC) has become routine. Recent studies indicated that plasma estradiol levels were related to expression levels of estrogen-responsive genes in ER-positive breast cancer tissues in both preand postmenopausal women. In this study, we analyzed expression levels of estrogen-responsive genes (PgR and TFF1), a progesterone-responsive gene (RANKL), ER-related genes (FOXA1 and GATA3), HER2, Ki67 and p53 in ER-positive, HER2-negative breast cancer tissues by IHC.Correlations between expression levels of these molecular markers and clinicopathological factors, including prognosis, were compared between pre-and postmenopausal women. Serum levels of estrone, estradiol, progesterone and testosterone were also measured. Expression levels of PgR, TFF1, RANKL and GATA3 were significantly higher in premenopausal women than in postmenopausal women. Serum estradiol levels were positively correlated with Ki67 labeling index (LI) in premenopausal women, but not in postmenopausal women. High expression of FOXA1 and GATA3 was significantly associated with improved disease-free survival in premenopausal women, but not in postmenopausal women, whereas high expression of PgR and low expression of p53 was significantly correlated with improved disease-free survival in postmenopausal women, but not in premenopausal women. Moreover, the best cutoff points of 3 Ki67 LI for disease-free survival were 30% for premenopausal women and 14% for postmenopausal women. Expression levels of ER, TFF1 and RANKL were not associated with disease-free survival in either pre-or postmenopausal women. Our results suggest that the mechanisms of development and estrogen-dependent growth of ER-positive breast cancer might differ according to menopausal status.

Comparative study of Her-2, p53, Ki-67 expression and clinicopathological characteristics of breast cancer in a cohort of northern China female patients

“…Mutations in the p53 genes cause the formation of stabilized proteins, which accumulate and can be analyzed by immunohistochemistry. 15,16 Our finding that p53 positive caused breast carcinoma to progress to a higher histological grade, which is in agreement with previous reports 37,48,49 and suggests that mutation in p53 genes have a tumor promotion role in breast cancer patients, 39 which is supported by previous reports. 37 Ki-67 is a nuclear protein that is commonly used for the detection and quantification of proliferating cells because an increase in its expression is associated with cell growth.…”

“…Mutation in the p53 genes causes the formation of stable proteins that can be analyzed by immunohistochemistry. 15,16 The detection of mutations in p53 genes in germline 30 suggests that they may be genetically inherited. Both the p53 gene and the Her-2 gene are located in chromosome 17.…”

“…Mutation in the p53 genes causes the formation of proteins that are more stable than the wild type protein; the mutant proteins accumulate and can be analyzed by immunohistochemistry. 15,16 The human p53 is a nuclear phosphoprotein composed of 393 amino acids. It represses or activates gene expression through binding at many sites of chromatin.…”

Diagnostic Value of ER, PR, FR and HER-2-Targeted Molecular Probes for Magnetic Resonance Imaging in Patients with Breast Cancer

“…First of all, ER is important for estrogen-dependent growth and can regulate the proliferation of both neoplastic breast and normal epithelial. In addition, the level of ER is regarded as a key factor determining the response to endocrine therapies and the prognosis in ER-positive breast cancer [14,33]. Estrogen affects the breast cancer primarily by its expression in tumor tissues.…”

Prognostic value of the ubiquitin ligase carboxyl terminus of the Hsc70‐interacting protein in postmenopausal breast cancer

“…In addition, it is well known that plasma estrogen levels of premenopausal women are significantly higher than that of postmenopausal women. Therefore, it is speculated that inhibitory effect of CHIP to breast cancer growth might be actualized more strongly in postmenopausal state because of condition of low plasma estrogen level 25.…”