Expression of estrogen receptors in tonsillar tissues of IgA nephropathy

• Project/Area Number: 17K08736
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Human pathology
• Research Institution: Yamagata University
• Principal Investigator: Yamakawa Mitsunori 山形大学, 医学部, 教授 (20183676)
• Project Period (FY): 2017-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2019: ¥260,000 (Direct Cost: ¥200,000、Indirect Cost: ¥60,000); Fiscal Year 2018: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000); Fiscal Year 2017: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: IgA腎症 / 口蓋扁桃 / リンパ上皮共生域 / 濾胞樹状細胞 / エストロゲン・レセプター / 胸腺間質リンホポイエチン / 扁桃 / エストロゲンレセプター-alpha / TSLP / IgA腎 / ER-α / 濾胞性リンパ腫 / 扁桃組織

Outline of Final Research Achievements

The present study has firstly demonstrated the expression of estrogen receptor (ER)-alpha on squamous epithelial cells in lymphoepithelial symbiosis areas (LSAs), the specific squamous epithelial layer containing lymphocytes, and follicular dendritic cells in follicular germinal centers of palatine tonsils. Furthermore, tonsillar LSAs in patients with IgA nephropathy, in which renal glomerular deposition of aberrantly glycosylated IgA and immune complex containing glycosylated IgA is found related to mucosal and tonsillar infection, more frequently expressed the ER-alpha, compared to those with non-IgA nephropathy. In addition, there was a well correlation between the expression of ER-alpha and thymic stromal lymphopoietin in the tonsillar LSAs, the latter being a positive regulator for IgA production in the follicular germinal centers in the palatine tonsils.

Academic Significance and Societal Importance of the Research Achievements

IgA腎症は慢性糸球体腎炎の主要な疾患で、治療法にはステロイドパルス療法、免疫抑制薬、口蓋扁桃摘出術（+ステロイドパルス併用療法）などの対象療法があるが、確立された有効な治療法はなく、透析や移植が必要な末期腎不全に至りやすい（成人発症例では20年間で約40%弱）。今回の研究で、扁桃のLSAの扁平上皮におけるER-alphaの発現が有意に高頻度で、IgA産生に関与するTSLPの発現と相関性が認められたことにより、難治性で予後不良な疾患であるIgA腎症に対して、TSLPやER-alphaに対する分子標的薬あるいは乳癌や子宮内膜癌などと同じような抗ホルモン療法が適応できうる可能性が示唆される。

Research Products

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• [Journal Article] A case of iatrogenic immunodeficiency-associated colonic lymphoma complicating ulcerative colitis (2020)
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  • Journal Title: Diagnostic Pathology Volume: 15 Issue: 1 Pages: 34-34
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• [Journal Article] Good Prognosis for Follicular Lymphoma with Estrogen Receptor α-positive Follicular Dendritic Cells (2020)
  • Author(s): Ohe Rintaro、Meng Hong-Xue、Yamada Akane、Aung Naing Ye、Kabasawa Takanobu、Tamura Yuka、Utsunomiya Aya、Tamazawa Nobuyuki、Kawamura Ichiro、Kitaoka Takumi、Suzuki Kazushi、Yanagiya Ryo、Toubai Tomomi、Ishizawa Kenichi、Yamakawa Mitsunori
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• [Journal Article] Primary Cutaneous Adenoid Cystic Carcinoma Connecting to the Epidermis (2019)
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  • Journal Title: The American Journal of Dermatopathology Volume: 41 Issue: 8 Pages: 619-621
  • DOI: 10.1097/dad.0000000000001179
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• [Journal Article] Differential expression of estrogen receptor-α on follicular dendritic cells from patients with grade 1-2 and grade 3 follicular lymphoma (2019)
  • Author(s): Ohe R, Meng HX, Ye Aung N, Yamada A, Kabasawa T, Utsunomiya A, Tamazawa N, Tamura Y, Kitaoka T, Hashimoto T, Shibata K, Toubai T, Kimura W, Ishizawa K, Yamakawa M
  • Journal Title: Hematol Oncol Volume: 37 Issue: 2 Pages: 151-159
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• [Journal Article] Expression of total and phosphor 4EBP1 in metastatic and non-metastatic renal cell carcinoma (2019)
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  • Journal Title: Oncol Lett Volume: 17 Pages: 3910-3918
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• [Journal Article] Impact of eIF4E phosphorylation at Ser209 via MNK2a on tumour recurrence after curative surgery in localized clear cell renal cell carcinoma (2019)
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  • DOI: 10.1159/000500225
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• [Journal Article] Effect of cold and hot compress on neutrophilic migration to the site of doxorubicin extravasation (2019)
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• [Journal Article] Diagnostic utility of CD205 in breast cancer: Simultaneous detection of myoepithelial cells and dendritic cells in breast tissue by CD205 (2019)
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  • Journal Title: Histol Histopathol Volume: 16
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• [Journal Article] Immunoglobulin G Subclass 4-Related Lymphoplasmacytic Thoracic Aortitis in a Patient with Acute Type A Aortic Dissection (2018)
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  • Journal Title: Annals of Thoracic and Cardiovascular Surgery Volume: 24 Issue: 4 Pages: 208-210
  • DOI: 10.5761/atcs.cr.17-00111
  • NAID: 130007437297
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• [Journal Article] Pathologic evaluation of tumor budding as a prognostic factor for Stage I-II tongue squamous cell carcinoma (2018)
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• [Journal Article] Detection of Minimal Bone Marrow involvement of Blastic Plasmacytoid Dendritic Cell Neoplastic Cells - CD303 immunostaining as a diagnostic tool- (2018)
  • Author(s): Ohe Rintaro、Aung Naing Ye、Shiono Yosuke、Utsunomiya Aya、Kabasawa Takanobu、Tamazawa Nobuyuki、Tamura Yuka、Kato Tomoya、Yamada Akane、Hasegawa Shin、Aizawa Keiko、Inokura Kyoko、Ito Satoshi、Toubai Tomomi、Kato Yuichi、Tsunoda Takahiko、Onami Kosuke、Suzuki Tamio、Ishizawa Kenichi、Yamakawa Mitsunori
  • Journal Title: Journal of Clinical and Experimental Hematopathology Volume: 58 Issue: 1 Pages: 1-9
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  • Journal Title: Hepatol Res Volume: 48 Issue: 12 Pages: 989-999
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• [Journal Article] Levels of 4EBP1/eIF4E activation in renal cell carcinoma could differentially predict its early and late recurrence (2018)
  • Author(s): Ichiyanagi O, Naito S, Ito H, Kabasawa T, Narisawa T, Kanno H, Kurota Y, Kurokawa M, Fukuhara H, Sakurai T, Nishida H, Kato T, Yamakawa M, Tsuchiya N
  • Journal Title: Clin Genitourin Cancer Volume: 16 Issue: 5 Pages: e1029-e1058
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• [Journal Article] Expression of TRPM8 in human reactive lymphoid tissues and mature B cell neoplasms (2018)
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• [Journal Article] Clonally related diffuse large B-cell lymphoma and interdigitating dendritic cell sarcoma sharing MYC translocation (2018)
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  • Journal Title: Haematologica Volume: 103 Issue: 11 Pages: e553-e556
  • DOI: 10.3324/haematol.2018.193490
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• [Journal Article] 9.病理診断: 術中迅速診断 (2018)
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• [Journal Article] Spontaneous Remission of Everolimus-Induced Interstitial Lung Disease in Metastatic Renal Cell Carcinoma : An Autopsy Case Report (2017)
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  • Journal Title: 泌尿器科紀要 Volume: 63 Issue: 9 Pages: 377-380
  • DOI: 10.14989/ActaUrolJap_63_9_377
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  • Year and Date: 2017-09-30
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• [Journal Article] Villous lymphocytes observed in the cerebrospinal fluid of a patient with asymptomatic neurosyphilis (2017)
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  • Journal Title: Nippon Shokakibyo Gakkai Zasshi Volume: 114 Issue: 6 Pages: 1023-1030
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• [Journal Article] Myoepithelial carcinoma of the breast with focal rhabdoid features (2013)
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  • Organizer: 第28回日本樹状細胞研究会
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  • Author(s): Naing YA, Tamazawa N, Utsunomiya A, Kabasawa T, Ohe R, Kato T, Yamakawa M
  • Organizer: 第57回日本リンパ網内系学会総会
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  • Author(s): 樺澤崇允, 山川光徳
  • Total Pages: 8
  • Publisher: 医薬ジャーナル社
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  • Author(s): 大江倫太郎, 山川光徳
  • Total Pages: 3
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  • ISBN: 9784830604799
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  • Author(s): 大江倫太郎, 山川光徳
  • Total Pages: 5
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  • Author(s): 大江倫太郎, 山川光徳
  • Total Pages: 4
  • Publisher: 文光堂
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  • Author(s): 大江倫太郎、山川光徳
  • Total Pages: 46
  • Publisher: 西村書店
  • ISBN: 9784890134786