Open AccessImmunohistochemical analysis‐based proteomic subclassification of newly diagnosed glioblastomas
Author(s) -
Motomura Kazuya,
Natsume Atsushi,
Watanabe Reiko,
Ito Ichiro,
Kato Yukinari,
Momota Hiroyuki,
Nishikawa Ryo,
Mishima Kazuhiko,
Nakasu Yoko,
Abe Tatsuya,
Namba Hiroki,
Nakazato Yoichi,
Tashiro Hiroshi,
Takeuchi Ichiro,
Mori Tsutomu,
Wakabayashi Toshihiko
Publication year - 2012
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/j.1349-7006.2012.02377.x
Subject(s) - pdgfra , biology , immunohistochemistry , dna methylation , idh1 , synaptophysin , pathology , oncology , cancer research , medicine , gene , gene expression , genetics , stromal cell , gist , mutation
Recent gene expression and copy number profilings of glioblastoma multiforme ( GBM ) by T he C ancer G enome A tlas ( TCGA ) R esearch N etwork suggest the existence of distinct subtypes of this tumor. However, these approaches might not be easily applicable in routine clinical practice. In the current study, we aimed to establish a proteomics‐based subclassification of GBM by integrating their genomic and epigenomic profiles. We subclassified 79 newly diagnosed GBM based on expression patterns determined by comprehensive immunohistochemical observation in combination with their DNA copy number and DNA methylation patterns. The clinical relevance of our classification was independently validated in TCGA datasets. Consensus clustering identified the four distinct GBM subtypes: O ligodendrocyte P recursor ( OPC ) type, D ifferentiated O ligodendrocyte ( DOC ) type, A strocytic M esenchymal ( A s M es) type and M ixed type. The OPC type was characterized by highly positive scores of O lig2, PDGFRA , p16, p53 and synaptophysin. In contrast, the A s M es type was strongly associated with strong expressions of nestin, CD 44 and podoplanin, with a high glial fibrillary acidic protein score. The median overall survival of OPC ‐type patients was significantly longer than that of the A s M es‐type patients (19.9 vs 12.8 months). This finding was in agreement with the O ncomine analysis of TCGA datasets, which revealed that PDGFRA and O lig2 were favorable prognostic factors and podoplanin and CD 44 were associated with a poor clinical outcome. This is the first study to establish a subclassification of GBM on the basis of immunohistochemical analysis. Our study will shed light on personalized therapies that might be feasible in daily neuropathological practice. ( Cancer Sci , doi: 10.1111/j.1349‐7006.2012.02377.x, 2012)