Alternative Title乳腺浸潤性小葉癌におけるN末端欠損E-カドヘリン蛋白の発現
Degree grantor/typeNagasaki University (長崎大学)
Note (General)Invasive lobular carcinoma (ILC) of the breast is characterized by the discohesive growth of tumor cells, which is mainly associated with the complete loss of E-cadherin (E-cad) expression. However, some aberrant expression patterns of E-cad protein that are inconsistent with their morphologies have been reported in ILC. We report herein ILC cases expressing a new type of abnormal E-cad protein that lacks the N-terminal domain, but conserves the C-terminal domain on the cell membrane. Immunohistochemical staining of 299 ILC cases using specific antibodies against the N-terminal or C-terminal region of E-cad revealed that 227 (76%) cases showed loss of the membranous expression of both terminuses (N−/C−) and 72 (24%) cases showed expression of only the C-terminus (N−/C+). In all cases, the expression of p120-catenin and β-catenin coincided with the expression of the C-terminus of E-cad. Clinicopathologic analysis revealed that N−/C+ expression in ILC cells was significantly associated with the histologic subtype (especially mixed-type ILC with another histologic type) and immunohistochemical molecular subtype (especially the triple-negative subtype), but not with prognostic factors (pT or pN). In addition, 12 of 15 cases (80%) with aberrant cytoplasmic localization of the N-terminal of E-cad showed diffuse membranous expression of the C-terminal domain. Additional immunohistochemistry using an antibody recognizing the extracellular juxtamembrane region showed that 28 (39%) of the N−/C+ cases had lost membranous expression, suggesting diversity in the deletion pattern of the N-terminal region. Our findings provide a novel mechanism for the loss of E-cad function because of N-terminal-deficient E-cad protein in ILC.
長崎大学学位論文 学位記番号:博(医歯薬)甲第1375号 学位授与年月日:令和3年12月1日
Author: Haruna Yasui, Takuya Kawata, Koji Muramatsu, Yuko Kakuda, Takuma Oishi, Tomoko Norose, Akifumi Notsu, Seiichiro Nishimura, Junya Fukuoka, Takashi Sugino
Citation: The American Journal of Surgical Pathology, doi: 10.1097/PAS.0000000000001822; 2021
identifier:Nagasaki University (長崎大学), 博士(医学) (2021-12-01)
http://hdl.handle.net/10069/00041136
Collection (particular)国立国会図書館デジタルコレクション > デジタル化資料 > 博士論文
Date Accepted (W3CDTF)2023-03-02T11:18:09+09:00
Data Provider (Database)国立国会図書館 : 国立国会図書館デジタルコレクション