title: Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas.
abstract: The great majority of invasive lobular carcinoma (ILC) is estrogen-dependent luminal A type carcinoma but the details of estrogen actions and its intratumoral metabolism have not been well studied compared to invasive ductal carcinoma (IDC). We first immunolocalized estrogen-related enzymes including estrogen sulfotransferase (EST), estrogen sulfatase (STS), 17β-hydroxysteroid dehydrogenase (HSD) 1/2, and aromatase. We then evaluated the tissue concentrations of estrogens in ILC and IDC and subsequently estrogen-responsive gene profiles in these tumors in order to explore the possible differences and/or similarity of intratumoral estrogen environment of these two breast cancer subtypes. The status of STS and 17βHSD1 was significantly lower in ILCs than IDCs (p = 0.022 and p < 0.0001), but that of EST and 17βHSD2 vice versa (p < 0.0001 and p = 0.0106). In ILCs, tissue concentrations of estrone and estradiol were lower than those in IDCs (p = 0.0709 and 0.069). In addition, the great majority of estrogen response genes tended to be lower in ILCs. Among those genes above, FOXP1 was significantly higher in ILCs than in IDCs (p = 0.002). FOXP1 expression was reported to be significantly higher in relapse-free IDC patients treated with tamoxifen. Therefore, tamoxifen may be considered an option of endocrine therapy for luminal A type ILC patients. This is the first study to demonstrate the detailed and comprehensive status of intratumoral production and metabolism of estrogens and the status of estrogen response genes in luminal A-like ILC with comparison to those in luminal A-like IDCs.
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan.
authors.forename: Mayu
authors.initials: M
authors.lastname: Takagi
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan. miki@patholo2.med.tohoku.ac.jp.
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Miki
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Minoru
authors.initials: M
authors.lastname: Miyashita
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan.
authors.forename: Shuko
authors.initials: S
authors.lastname: Hata
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan.
authors.forename: Tomomi
authors.initials: T
authors.lastname: Yoda
authors.affiliation: Department of Breast Surgery, Tohoku Kosai Hospital, Sendai, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hirakawa
authors.affiliation: Department of Breast Surgical Oncology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Sagara
authors.affiliation: Department of Breast Surgical Oncology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan.
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Rai
authors.affiliation: Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan.
authors.forename: Yasuyo
authors.initials: Y
authors.lastname: Ohi
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.|Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan.
authors.forename: Kentaro
authors.initials: K
authors.lastname: Tamaki
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Takanori
authors.initials: T
authors.lastname: Ishida
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan.
authors.forename: Noriaki
authors.initials: N
authors.lastname: Ouchi
authors.affiliation: Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan.
authors.forename: Hironobu
authors.initials: H
authors.lastname: Sasano
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000378:metabolism; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001141:Aromatase / Q000378:metabolism; D001943:Breast Neoplasms / Q000378:metabolism* / Q000473:pathology; D018270:Carcinoma, Ductal, Breast / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018275:Carcinoma, Lobular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D004967:Estrogens / Q000096:biosynthesis*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008875:Middle Aged; D012097:Repressor Proteins / Q000235:genetics; D013429:Sulfatases / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism
chemical_list: D004967:Estrogens; C486626:FOXP1 protein, human; D051858:Forkhead Transcription Factors; D012097:Repressor Proteins; D015067:17-Hydroxysteroid Dehydrogenases; C044256:3 (or 17)-beta-hydroxysteroid dehydrogenase; D001141:Aromatase; D015238:Sulfotransferases; C020122:estrone sulfotransferase; D013429:Sulfatases; C039596:estrogen sulfatase
keywords: FOXP1; Intracrine; Invasive ductal carcinoma; Invasive lobular carcinoma