PMID- 36063222 OWN - NLM STAT- MEDLINE DCOM- 20230719 LR - 20230719 IS - 1432-1335 (Electronic) IS - 0171-5216 (Linking) VI - 149 IP - 8 DP - 2023 Jul TI - Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma. PG - 4253-4267 LID - 10.1007/s00432-022-04336-z [doi] AB - 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. CI - (c) 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature. FAU - Shayanfar, Nasrin AU - Shayanfar N AD - Department of Pathology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran. FAU - Zare-Mirzaie, Ali AU - Zare-Mirzaie A AD - Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. FAU - Mohammadpour, Mahsa AU - Mohammadpour M AD - Department of Medical School, Tehran University of Medical Sciences, Tehran, Iran. FAU - Jafari, Ensieh AU - Jafari E AD - Department of Biology, Faculty of Basic Science, Noor Danesh University, Isfahan, Iran. FAU - Mehrtash, Amirhosein AU - Mehrtash A AD - Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran. FAU - Emtiazi, Nikoo AU - Emtiazi N AD - Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran. Nikooemtiazi9@gmail.com. FAU - Tajik, Fatemeh AU - Tajik F AD - Oncopathology Research Center, Iran University of Medical Sciences, Tehran, Iran. efateme_tajik@yahoo.com. LA - eng GR - Grant Number# 19921/Iran University of Medical Sciences/ PT - Journal Article DEP - 20220905 PL - Germany TA - J Cancer Res Clin Oncol JT - Journal of cancer research and clinical oncology JID - 7902060 RN - EC 1.1.1.41 (Isocitrate Dehydrogenase) RN - EC 1.1.1.42. (IDH1 protein, human) SB - IM MH - Humans MH - *Glioma/pathology MH - Isocitrate Dehydrogenase/genetics/metabolism MH - Squamous Cell Carcinoma of Head and Neck MH - Mutation MH - *Brain Neoplasms/pathology MH - *Head and Neck Neoplasms OTO - NOTNLM OT - Immunohistochemistry (IHC) OT - Isocitrate dehydrogenase 1 (IDH1) OT - Laryngeal squamous cell carcinoma (LSCC) OT - Polymerase chain reaction (PCR) OT - Tissue microarray (TMA) EDAT- 2022/09/06 06:00 MHDA- 2023/07/19 06:43 CRDT- 2022/09/05 11:15 PHST- 2022/07/22 00:00 [received] PHST- 2022/08/26 00:00 [accepted] PHST- 2023/07/19 06:43 [medline] PHST- 2022/09/06 06:00 [pubmed] PHST- 2022/09/05 11:15 [entrez] AID - 10.1007/s00432-022-04336-z [pii] AID - 10.1007/s00432-022-04336-z [doi] PST - ppublish SO - J Cancer Res Clin Oncol. 2023 Jul;149(8):4253-4267. doi: 10.1007/s00432-022-04336-z. Epub 2022 Sep 5.