title: 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 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 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 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 disease-free 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 postmenopausal women, but not in premenopausal women. 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 of ER-positive breast cancer might differ according to menopausal status.
authors.affiliation: Breast and Endocrine Surgery, Hokkaido University Hospital, Kita 14 Nishi 5, Kita-ku, Sapporo, 060-8648, Japan.
authors.forename: Mitsuchika
authors.initials: M
authors.lastname: Hosoda
authors.forename: Mitsugu
authors.initials: M
authors.lastname: Yamamoto
authors.forename: Kiichiroh
authors.initials: K
authors.lastname: Nakano
authors.forename: Kanako C
authors.initials: KC
authors.lastname: Hatanaka
authors.forename: Emi
authors.initials: E
authors.lastname: Takakuwa
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hatanaka
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Matsuno
authors.forename: Hiroko
authors.initials: H
authors.lastname: Yamashita
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001943:Breast Neoplasms / Q000097:blood* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D004958:Estradiol / Q000097:blood; D004970:Estrone / Q000097:blood; D005260:Female; D050990:GATA3 Transcription Factor / Q000096:biosynthesis* / Q000235:genetics; D015870:Gene Expression; D051541:Hepatocyte Nuclear Factor 3-alpha / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D019394:Ki-67 Antigen / Q000096:biosynthesis / Q000235:genetics; D008875:Middle Aged; D017698:Postmenopause / Q000097:blood; D017697:Premenopause / Q000097:blood; D011374:Progesterone / Q000097:blood; D011379:Prognosis; D053245:RANK Ligand / Q000235:genetics; D011960:Receptors, Estrogen / Q000096:biosynthesis* / Q000235:genetics; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D013739:Testosterone / Q000097:blood; D000071163:Trefoil Factor-1; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis* / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: C496499:FOXA1 protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D051541:Hepatocyte Nuclear Factor 3-alpha; D019394:Ki-67 Antigen; D053245:RANK Ligand; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; C051838:TFF1 protein, human; C505688:TNFSF11 protein, human; C495901:TP53 protein, human; D000071163:Trefoil Factor-1; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D004970:Estrone; D013739:Testosterone; D011374:Progesterone; D004958:Estradiol