論文

査読有り
2016年5月

Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes

AMERICAN JOURNAL OF PATHOLOGY
  • Ryusuke Murakami
  • Noriomi Matsumura
  • Masaki Mandai
  • Kosuke Yoshihara
  • Hiroshi Tanabe
  • Hidekatsu Nakai
  • Koji Yamanoi
  • Kaoru Abiko
  • Yumiko Yoshioka
  • Junzo Hamanishi
  • Ken Yamaguchi
  • Tsukasa Baba
  • Masafumi Koshiyama
  • Takayuki Enomoto
  • Aikou Okamoto
  • Susan K. Murphy
  • Seiichi Mori
  • Yoshiki Mikami
  • Sachiko Minamiguchi
  • Ikuo Konishi
  • 全て表示

186
5
開始ページ
1103
終了ページ
1113
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1016/j.ajpath.2015.12.029
出版者・発行元
ELSEVIER SCIENCE INC

Recently, The Cancer Genome Atlas data revealed four molecular subtypes of high-grade serous ovarian carcinoma (HGSOC) exhibiting distinct prognoses. We developed four novel HGSOC histopathological subtypes by focusing on tumor microenvironment: mesenchymal transition, defined by a remarkable desmoplastic reaction; immune reactive by lymphocytes infiltrating the tumor; solid and proliferative by a solid growth pattern; and papilloglandular by a papillary architecture. Unsupervised hierarchical clustering revealed four clusters correlated with histopathological subtypes in both Kyoto and Niigata HGSOC transcriptome data sets (P < 0.001). Gene set enrichment analysis revealed pathways enriched in our histopathological classification significantly overlapped with the four molecular subtypes: mesenchymal, immunoreactive, proliferative, and differentiated (P < 0.0001, respectively). In 132 HGSOC cases, progression-free survival and overall survival were best in the immune reactive, whereas overall survival was worst in the mesenchymal transition (P < 0.001, respectively), findings reproduced in 89 validation cases (P < 0.05, respectively). The CLOVAR_MES_UP single-sample gene set enrichment analysis scores representing the mesenchymal molecular subtype were higher in paclitaxel responders than nonresponders (P = 0.002) in the GSE15622 data set. Taxane-containing regimens improved survival of cases with high MES_UP scores compared with nontaxane regimens (P < 0.001) in the GSE9891 data set. Our novel histopathological classification of HGSOC correlates with distinct prognostic transcriptome subtypes. The mesenchymal transition subtype might be particularly sensitive to taxane.

リンク情報
DOI
https://doi.org/10.1016/j.ajpath.2015.12.029
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26993207
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000375334700005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1016/j.ajpath.2015.12.029
  • ISSN : 0002-9440
  • eISSN : 1525-2191
  • PubMed ID : 26993207
  • Web of Science ID : WOS:000375334700005

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