Investigation of molecular markers for prediction of the highly aggressive breast cancers that show clinically progressive disease during neoadjuvant chemotherapy

2016 Fiscal Year Final Research Report

• Project/Area Number: 25430144
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor diagnostics
• Research Institution: National Defense Medical College
• Principal Investigator: TSUDA HITOSHI 防衛医科大学校(医学教育部医学科進学課程及び専門課程、動物実験施設、共同利用研究, 病態病理学, 教授 (70217321)
• Research Collaborator: Yoshida Masayuki 国立がん研究センター中央病院, 病理科・臨床検査科 ; Kinoshita Takayuki 国立がん研究センター中央病院, 乳腺外科, 科長 ; Tamura Kenji 国立がん研究センター中央病院, 乳腺・腫瘍内科, 科長 ; Ono Makiko 国立がん研究センター中央病院, 乳腺・腫瘍内科 ; Tanabe Yuko 国立がん研究センター中央病院, 乳腺・腫瘍内科
• Project Period (FY): 2013-04-01 – 2017-03-31
• Keywords: 乳癌 / 化学療法抵抗性 / 上皮間葉移行 / トリプルネガティブ乳癌 / 術前化学療法 / 臨床的病状進行

Outline of Final Research Achievements

Using surgically resected tumor specimens from 22 TNBCs that showed cPD during NAC (cPD group) and 80 TNBCs that did not receive NAC (control group), we performed histopathologic and immunohistochemical (IHC) analyses of 11 molecules relevant to epithelial-mesenchymal transition (EMT), basal-like, molecular apocrine or other features. Metaplastic features and high proliferation on histology and positive cytokeratin 5/6, ZEB1, TWISTNB, vimentin, and HMGB1 and negative androgen receptor (AR) by IHC were more frequent in the cPD than in the control. By an unsupervised hierarchical cluster analysis incorporating these 11 molecules, the 102 TNBCs were divided into two major clusters and seven subclusters that appeared to correspond to intrinsic subtype, cPD status, histological type, and clinical outcome. The combinations of high proliferation, metaplastic features, and statuses of some EMT and basal-like markers and AR appeared to characterize the TNBCs that showed cPD after NAC.

Free Research Field

腫瘍診断学