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Immunohistochemical staining of phosphorylated-ERK in post-chemotherapeutic samples is a potential predictor of the prognosis of neuroblastoma

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Abstract

Purpose

The majority of relapsed neuroblastomas have mitogen-activated protein kinase (MAPK) pathway activating mutations. We previously showed the in vitro and in vivo anti-tumor effects of MAPK/ERK kinase (MEK) inhibitors in MAPK-activated neuroblastoma. We herein assessed the correlation between MAPK activation and the prognosis in neuroblastoma patients using phosphorylated extra-cellular signal-regulated kinase (pERK) immunohistochemistry to establish the protocol for the clinical administration of MEK inhibitors.

Methods

Neuroblastoma samples from patients treated in our hospital were immunostained with pERK. The clinical outcomes were retrospectively collected from medical records. The correlation between pERK positivity and the prognosis was analyzed.

Results

Regarding pre-chemotherapeutic specimens, there were no differences in the pERK status between tumors with a good and bad prognosis in both the nuclei and cytoplasm. Regarding post-chemotherapeutic specimens, one of eight tumors with a good prognosis and four of six tumors with a poor prognosis showed pERK-positive nuclear staining (p = 0.0909) and five of eight tumors with a good prognosis and four of six tumors with a poor prognosis showed pERK-positive cytoplasmic staining (p > 0.9999).

Conclusion

These findings suggested post-chemotherapeutic—not pre-chemotherapeutic—nuclear pERK-positive neuroblastoma tends to be associated with a poor prognosis and may be a potential therapeutic target for MEK inhibitor treatment.

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Acknowledgements

This work was supported by Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology of Japan (MEXT KAKENHI Grant No. 19H03719) and by the Practical Research for Innovative Cancer Control from the Japan Agency for Medical Research and Development, AMED (Grant No. 19ck0106332h0003). The English of this manuscript was reviewed by Dr. Brian Quinn (Editor-in-Chief, Japan Medical Communication).

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Authors and Affiliations

  1. Department of Pediatric Surgery, Kyoto Prefectural University of Medicine, 465 Kajii-cho, Kamigyo-ku, Kyoto, 602-8566, Japan

    Tomoko Tanaka, Yuichi Togashi, Yuki Takeuchi, Mayumi Higashi, Shigehisa Fumino & Tatsuro Tajiri

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  1. Tomoko Tanaka
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  2. Yuichi Togashi
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  3. Yuki Takeuchi
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  4. Mayumi Higashi
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  5. Shigehisa Fumino
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  6. Tatsuro Tajiri
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Correspondence to Tomoko Tanaka.

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Tanaka, T., Togashi, Y., Takeuchi, Y. et al. Immunohistochemical staining of phosphorylated-ERK in post-chemotherapeutic samples is a potential predictor of the prognosis of neuroblastoma. Pediatr Surg Int 37, 287–291 (2021). https://doi.org/10.1007/s00383-020-04806-w

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  • DOI: https://doi.org/10.1007/s00383-020-04806-w

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