In-house molecular diagnosis of diffuse glioma updating the revised WHO classification by a platform of the advanced medical care system, Senshin-Iryo

Nobuhiro Hata; Yutaka Fujioka; Ryosuke Otsuji; Daisuke Kuga; Ryusuke Hatae; Yuhei Sangatsuda; Takeo Amemiya; Naoki Noguchi; Aki Sako; Minoru Fujiki; Masahiro Mizoguchi; Koji Yoshimoto

doi:10.1111/neup.12970

In-house molecular diagnosis of diffuse glioma updating the revised WHO classification by a platform of the advanced medical care system, Senshin-Iryo

Neuropathology. 2024 Mar 13. doi: 10.1111/neup.12970. Online ahead of print.

Authors

Nobuhiro Hata^{1

2}, Yutaka Fujioka¹, Ryosuke Otsuji¹, Daisuke Kuga¹, Ryusuke Hatae¹, Yuhei Sangatsuda¹, Takeo Amemiya^{1

3}, Naoki Noguchi¹, Aki Sako¹, Minoru Fujiki², Masahiro Mizoguchi^{1

3}, Koji Yoshimoto¹

Affiliations

¹ Department of Neurosurgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan.
² Department of Neurosurgery, Oita University Faculty of Medicine, Yufu, Japan.
³ Department of Neurosurgery, National Hospital Organization Kyushu Medical Center, Clinical Research Institute, Fukuoka, Japan.

PMID: 38477051
DOI: 10.1111/neup.12970

Abstract

Since the World Health Organization (WHO) 2016 revision, the number of molecular markers required for diffuse gliomas has increased, placing a burden on clinical practice. We have established an in-house, molecular diagnostic platform using Senshin-Iryo, a feature of Japan's unique healthcare system, and partially modified the analysis method in accordance with the WHO 2021 revision. Herein, we review over a total 5 years of achievements using this platform. Analyses of IDH, BRAF, and H3 point mutations, loss of heterozygosity (LOH) on 1p/19q and chromosomes 10 and 17, and MGMT methylation were combined into a set that was submitted to Senshin-Iryo as "Drug resistance gene testing for anticancer chemotherapy" and was approved in August 2018. Subsequently, in October 2021, Sanger sequencing for the TERT promoter mutation was added to the set, and LOH analysis was replaced with multiplex ligation-dependent probe amplification (MLPA) to analyze 1p/19q codeletion and newly required genetic markers, such as EGFR, PTEN, and CDKN2A from WHO 2021. Among the over 200 cases included, 54 were analyzed after the WHO 2021 revision. The laboratory has maintained a diagnostic platform where molecular diagnoses are confirmed within 2 weeks. Initial expenditures exceeded the income from patient copayments; however, it has gradually been reduced to running costs alone and is approaching profitability. After the WHO 2021 revision, diagnoses were confirmed using molecular markers obtained from Senshin-Iryo in 38 of 54 cases (70.1%). Among the remaining 16 patients, only four (7.4%) were diagnosed with diffuse glioma, not elsewhere classified, which was excluded in 12 cases where glioblastoma was confirmed by histopathological diagnosis. Our Senshin-Iryo trial functioned as a salvage system to overcome the transition period between continued revisions of WHO classification that has caused a clinical dilemma in the Japanese healthcare system.

Keywords: Senshin-Iryo; WHO 2016; WHO 2021; glioma; molecular pathology.

Abstract

Grants and funding