BEND2 Immunohistochemistry as a Useful Diagnostic Marker for Astroblastomas With BEND2 Fusion

Astroblastoma, MN1-altered, is a newly recognized entity in the 5th edition of the WHO Classification of CNS Tumors. Its genetic definition is the presence of an alteration, most commonly gene fusions, in the MN1 gene, with BEND2 being the most frequent fusion partner. However, some astroblastomas and astroblastoma-like tumors with fusion of non-MN1 to BEND2 have been reported recently. These tumors exhibit epigenetic profiles similar to those of astroblastomas with MN1::BEND2, suggesting that BEND2 may play a more important role than MN1 in tumorigenesis. Therefore, investigation of BEND2 fusion will be essential to make an accurate diagnosis of astroblastomas in the near future. In this study, we aimed to explore the diagnostic utility of BEND2 immunohistochemistry using a commercially available rabbit polyclonal antibody. As a result, nuclear expression of BEND2 was observed in all 15 cases of astroblastomas with BEND2 fusion (9 with MN1::BEND2, 4 with EWSR1::BEND2, 1 with MAMLD1::BEND2, and 1 with TCF3::BEND2), whereas it was not found in 147 cases of other CNS tumors from 48 different entities. In contrast, negative nuclear staining for BEND2 was observed in a previously reported case of spindle cell sarcoma with MN1::BEND2, whose fusion junction differed from those of the astroblastomas analyzed in this study. In conclusion, we demonstrated that BEND2 immunohistochemistry has extremely high sensitivity and specificity, suggesting its utility as a reliable marker for the diagnosis of astroblastoma with BEND2 fusion.

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Journal
The American Journal of Surgical Pathology
Published
2026-03-13
DOI
https://doi.org/10.1097/pas.0000000000002529
Primary Topic
Neuroblastoma Research and Treatments
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article
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article

BEND2 Immunohistochemistry as a Useful Diagnostic Marker for Astroblastomas With BEND2 Fusion

Akira Gomi, Akira Sasaki, Yasuhito Arai, Mitsuto Hanihara et al.
The American Journal of Surgical Pathology
Neuroblastoma Research and Treatments
article

BEND2 Immunohistochemistry as a Useful Diagnostic Marker for Astroblastomas With BEND2 Fusion

Akira Gomi, Akira Sasaki, Yasuhito Arai, Mitsuto Hanihara, Junko Hirato, Haruna Okuno, Yoshihiro Otani, Sumihito Nobusawa, Ayako Yamazaki, Masaya Nagaishi, Hirotaka Fudaba, Takanori Hirose, Mari Kirishima, Hironori Goto, Kana Washio, Seiji Tanaka, Seiji Yamada, Nozomi Matsumura, Hadzki Matsuda, Natsuko Hama, Takahiro Shirakura, Fumiyuki Yamasaki, Atsushi Ishida, Ryuta Saito, Eiichi Ishikawa, Hiromichi Suzuki, Yoshiki Mikami, Mitsutoshi Nakada, Hideaki Yokoo, Takuma Nakashima, Akihiko Yoshida, Yoshiki Arakawa, Tatsuhiro Shibata, Kai Yamasaki, Akitake Mukasa, Takako Yoshioka
article en

Abstract

Astroblastoma, MN1-altered, is a newly recognized entity in the 5th edition of the WHO Classification of CNS Tumors. Its genetic definition is the presence of an alteration, most commonly gene fusions, in the MN1 gene, with BEND2 being the most frequent fusion partner. However, some astroblastomas and astroblastoma-like tumors with fusion of non-MN1 to BEND2 have been reported recently. These tumors exhibit epigenetic profiles similar to those of astroblastomas with MN1::BEND2, suggesting that BEND2 may play a more important role than MN1 in tumorigenesis. Therefore, investigation of BEND2 fusion will be essential to make an accurate diagnosis of astroblastomas in the near future. In this study, we aimed to explore the diagnostic utility of BEND2 immunohistochemistry using a commercially available rabbit polyclonal antibody. As a result, nuclear expression of BEND2 was observed in all 15 cases of astroblastomas with BEND2 fusion (9 with MN1::BEND2, 4 with EWSR1::BEND2, 1 with MAMLD1::BEND2, and 1 with TCF3::BEND2), whereas it was not found in 147 cases of other CNS tumors from 48 different entities. In contrast, negative nuclear staining for BEND2 was observed in a previously reported case of spindle cell sarcoma with MN1::BEND2, whose fusion junction differed from those of the astroblastomas analyzed in this study. In conclusion, we demonstrated that BEND2 immunohistochemistry has extremely high sensitivity and specificity, suggesting its utility as a reliable marker for the diagnosis of astroblastoma with BEND2 fusion.

The American Journal of Surgical Pathology
Kanazawa University (JP), Kagoshima University (JP), Hiroshima University (JP), Fujita Health University (JP), University of Tsukuba (JP), Jichi Medical University (JP), Okayama University (JP), Gunma University (JP), Oita University (JP), Hokkaido University (JP), Kyoto University (JP), National Cancer Center (US), Osaka City General Hospital (JP), Okayama University Hospital (JP), University of Yamanashi Hospital (JP), Saitama Medical University Hospital (JP), Cancer Clinic (US), Kumamoto University Hospital (JP), Himeji Medical Center (JP), National Center For Child Health and Development (JP), Dokkyo Medical University Saitama Medical Center (JP), Hokkaido University Hospital (JP), Neurological Surgery (US), Gunma University Hospital (JP), Nagoya University (JP), University of Yamanashi (JP), Dokkyo Medical University (JP), Saitama Medical University (JP), Kumamoto University (JP)
Openalex Percentile: Top 30%
Neuroblastoma Research and Treatments
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