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Revisiting vimentin: a negative surrogate marker of molecularly defined oligodendroglioma in adult type diffuse glioma

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Abstract

Vimentin is a marker of epithelial-mesenchymal transformation and indicates poor prognosis in various cancers, but its role in diffuse gliomas remains unknown. We investigated the vimentin expression of diffuse gliomas according to the upcoming 2021 WHO classification, its variations due to mutational status, and its prognostic effects. We analyzed vimentin immunohistochemistry in 315 gliomas: a test set (n = 164) and a validation set (n = 151). RNA-seq and mutational information from The Cancer Genome Atlas (TCGA, n = 422) were also used for validation. Vimentin was diffusely positive in astrocytic tumors but negative in oligodendroglial tumors (ODGs) and its expression was significantly higher in isocitrate dehydrogenase (IDH) wild-type tumors. High vimentin expression was correlated with poor prognosis (hazard ratio [HR]: 5.99), but it was dependent on the new WHO grade which reflects both histologic features and genetics (HR: 1.28). Using the significant difference in vimentin expression between ODGs and astrocytic tumors, the positive and negative predictive values of the vimentin-based diagnosis for ODGs were 93.5% and 97.8% in the validation set. Along with additional alpha-thalassemia/mental retardation, X-linked (ATRX) immunohistostaining, the values were 98.3% and 97.8%, respectively. Vimentin is a useful ancillary marker for identifying ODGs when combined with routine histochemistry markers.

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Acknowledgements

This study was supported by a grant from Korea Health Technology R&D Project through the Korea Health Industry Development Institute, funded by the Ministry of Health and Welfare, Republic of Korea [grant no. HI14C1277] and the National Cancer Center, Republic of Korea (NCC-1810861-1).

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Author notes

  1. Seong-Ik Kim and Kwanghoon Lee have contributed equally.

Authors and Affiliations

  1. Department of Pathology, Seoul National University Hospital, College of Medicine, 103 Daehak-ro, Jongno-gu, Seoul, 110-799, South Korea

    Seong-Ik Kim, Kwanghoon Lee, Jeongmo Bae, Christopher Alec Maquiling, Sung-Hye Park & Jae-Kyung Won

  2. Center for Precision Medicine, Seoul National University Hospital, Seoul, 03080, South Korea

    Sungyoung Lee & Hongseok Yun

  3. Department of Neurosurgery, Seoul National University Hospital, College of Medicine, Seoul, 03080, South Korea

    Chul-Kee Park

  4. Department of Radiology, Seoul National University Hospital, College of Medicine, Seoul, 03080, South Korea

    Seung Hong Choi

  5. Neuroscience Institute, Seoul National University College of Medicine, Seoul, 03080, South Korea

    Sung-Hye Park

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Contributions

J-KW and S-HP designed the study. J-KW, S-IK, and S-HP reviewed histologic slides, drew annotations and acquired data for qualitative analysis. KL acquired data for quantitative analysis using positive pixel count v9 algorithm. C-KP and SHC carried out acquisition and analysis of clinical data. SL and HY acquired data from targeted brain tumor-related gene panel sequencing. S-IK and KL performed statistical analysis. S-IK, KL, JB, SL, HY, S-HP, and J-KW wrote the manuscript. All authors reviewed and edited the final manuscript.

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Correspondence to Jae-Kyung Won.

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Kim, SI., Lee, K., Bae, J. et al. Revisiting vimentin: a negative surrogate marker of molecularly defined oligodendroglioma in adult type diffuse glioma. Brain Tumor Pathol 38, 271–282 (2021). https://doi.org/10.1007/s10014-021-00411-4

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