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

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Title: Differential expression of progesterone receptor, FOXA1, GATA3, and p53 between pre- and postmenopausal women with estrogen receptor-positive breast cancer
Authors: Hosoda, Mitsuchika Browse this author →KAKEN DB
Yamamoto, Mitsugu Browse this author
Nakano, Kiichiroh Browse this author
Hatanaka, Kanako C. Browse this author
Takakuwa, Emi Browse this author
Hatanaka, Yutaka Browse this author →KAKEN DB
Matsuno, Yoshihiro Browse this author
Yamashita, Hiroko Browse this author →KAKEN DB
Keywords: Breast cancer
Progesterone receptor
Issue Date: Apr-2014
Publisher: Springer
Journal Title: Breast Cancer Research and Treatment
Volume: 144
Issue: 2
Start Page: 249
End Page: 261
Publisher DOI: 10.1007/s10549-014-2867-0
PMID: 24549642
Abstract: Estrogen receptor (ER) is essential for estrogendependent 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 levelswere related to the expression levels of estrogen-responsive genes in ER-positive breast cancer tissues in both pre- and postmenopausal women. In this study, we analyzed the expression levels of strogenresponsive 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 the 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 diseasefree survival in premenopausal women, but not in postmenopausal women, whereas high expression of PgR and low expression of p53 were significantly correlated with the improved disease-free survival in postmenopausalwomen, but not in premenopausalwomen.Moreover, the best cutoff points of 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 the disease-free survival in either pre- or postmenopausal women. Our results suggest that the mechanisms of development and estrogen-dependent growth ofER-positive breast cancer might differ according to menopausal status.
Rights: The final publication is available at
Type: article (author version)
Appears in Collections:北海道大学病院 (Hokkaido University Hospital) > 雑誌発表論文等 (Peer-reviewed Journal Articles, etc)

Submitter: 山下 啓子

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