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Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas

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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.

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Authors and Affiliations

  1. Department of Surgical Oncology, Tohoku University Graduate School of Medicine, Sendai, Japan

    Mayu Takagi, Minoru Miyashita, Kentaro Tamaki, Takanori Ishida & Noriaki Ouchi

  2. Department of Pathology, Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi Aoba-ku, Sendai, Japan

    Mayu Takagi, Yasuhiro Miki, Shuko Hata, Tomomi Yoda, Kentaro Tamaki, Takashi Suzuki & Hironobu Sasano

  3. Department of Breast Surgery, Tohoku Kosai Hospital, Sendai, Japan

    Hisashi Hirakawa

  4. Department of Breast Surgical Oncology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan

    Yasuaki Sagara & Yoshiaki Rai

  5. Department of Pathology, Sagara Hospital, Social Medical Corporation Hakuaikai, Kagoshima, Japan

    Yasuyo Ohi

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  1. Mayu Takagi
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Correspondence to Yasuhiro Miki.

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10549_2016_3739_MOESM1_ESM.pptx

Supplemental Fig. 1. Relationship between intratumoral estrone concentration and intracrine-related enzymes in ILC and IDC. Expressions of intracrine-related enzymes were evaluated by immunohistochemistry. 17βHSD1 was not detected in IDC. Supplemental Fig. 2. Relationship between intratumoral estradiol concentration and intracrine-related enzymes in ILC and IDC. Expressions of intracrine-related enzymes were evaluated by immunohistochemistry. 17βHSD1 was not detected in IDC. Supplementary material 1 (PPTX 83 kb)

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Takagi, M., Miki, Y., Miyashita, M. et al. Intratumoral estrogen production and actions in luminal A type invasive lobular and ductal carcinomas. Breast Cancer Res Treat 156, 45–55 (2016). https://doi.org/10.1007/s10549-016-3739-6

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  • DOI: https://doi.org/10.1007/s10549-016-3739-6

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