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Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma

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Abstract

Introduction

Recent developments in genomic sequencing have led to the identification of somatic mutations in isocitrate dehydrogenase 1 (IDH1) in various malignancies. IDH1 R132H is the most common mutation of IDH1, which affects codon 132 and results in the conversion of amino acid residue arginine (R) to histidine (H). This study is designed to evaluate the association between the expression of IDH1 R132H and clinicopathological characteristics in laryngeal squamous cell carcinoma (LSCC).

Methods

The expression pattern and clinical significance of IDH1 R132H were investigated in tissue microarrays (TMAs) of 50 LSCC tumors as well as adjacent normal tissues using immunohistochemistry. Then the exons of the 12 tumor samples with negative/weak positive staining were sequenced by applying polymerase chain reaction (PCR).

Results

The results demonstrated that the cytoplasmic expression of IDH1 R132H was downregulated in tumor cells compared to adjacent normal tissues. A statistically significant association was found between a low level of cytoplasmic expression of IDH1 R132H protein and an increase in histological grade (p < 0.001), perineural invasion (p = 0.019), and lymph node involvement (p < 0.001). The exon4 sequencing results showed that only one sample was positive for IDH1 R132H mutation. IDH1 R132H expression was observed in 39 (78.0%) LSCC samples.

Conclusion

These findings indicate that low cytoplasmic expression of IDH1 R132H may have clinical significance in LSCC patients and is associated with more aggressive tumor behavior and progression of the disease, which can help improve potential treatment in patients with LSCC. Further investigations are needed to understand the biological function of IDH1 R132H and larger sample size to confirm our findings.

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Availability of data and materials

The analyzed data during the current study are available from the corresponding author on reasonable request.

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Funding

This study was conducted as part of a resident thesis and was financially supported by a grant from the Department of Pathology, Iran University of Medical Sciences (IUMS; Grant No. 19921).

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Authors and Affiliations

  1. Department of Pathology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran

    Nasrin Shayanfar

  2. Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

    Ali Zare-Mirzaie & Nikoo Emtiazi

  3. Department of Medical School, Tehran University of Medical Sciences, Tehran, Iran

    Mahsa Mohammadpour

  4. Department of Biology, Faculty of Basic Science, Noor Danesh University, Isfahan, Iran

    Ensieh Jafari

  5. Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

    Amirhosein Mehrtash

  6. Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran

    Fatemeh Tajik

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  1. Nasrin Shayanfar
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Contributions

N.Sh., N.E., and F.T. designed and supervised the project, rechecked and approved all parts of the manuscript, and performed data analysis. N.E. and F.T. wrote the manuscript. M.M. and A.M. collected the paraffin-embedded tissues, collected the patient data, and performed an IHC experiment. A.Z.M. analyzed and interpreted the SPSS data and helped to prepare the tables. N.Sh. marked the most representative areas in different parts of the tumor for the construction of TMAs blocks and scored TMAs slides after IHC staining, and helped to prepare the figures. E.J. performed PCR and analyzed the results of PCR. All authors read and approved the final manuscript.

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Correspondence to Nikoo Emtiazi or Fatemeh Tajik.

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All procedures performed in this study were in line with the ethical standards of the institution at which this study was conducted. Informed consent was individually obtained from all participants. The Research Ethics Committee of Iran University of Medical Sciences issued IR.IUMS.FMD.REC.1399.276 for this study.

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Informed consent was obtained from all individual participants, parents, or legally authorized representatives of participants below the legal age limit at the time of sample collection with routine consent forms.

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Shayanfar, N., Zare-Mirzaie, A., Mohammadpour, M. et al. Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma. J Cancer Res Clin Oncol 149, 4253–4267 (2023). https://doi.org/10.1007/s00432-022-04336-z

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