Establishment of a Novel Histopathological Classification of High-Grade Serous Ovarian Carcinoma Correlated with Prognostically Distinct Gene Expression Subtypes
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, 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
Abstract
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.
Copyright © 2016 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.
Source: PubMed