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

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 arginin...

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Published in:Journal of cancer research and clinical oncology 2023-07, Vol.149 (8), p.4253-4267
Main Authors: Shayanfar, Nasrin, Zare-Mirzaie, Ali, Mohammadpour, Mahsa, Jafari, Ensieh, Mehrtash, Amirhosein, Emtiazi, Nikoo, Tajik, Fatemeh
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container_title Journal of cancer research and clinical oncology
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creator Shayanfar, Nasrin
Zare-Mirzaie, Ali
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Tajik, Fatemeh
description 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  
doi_str_mv 10.1007/s00432-022-04336-z
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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  &lt; 0.001), perineural invasion ( p  = 0.019), and lymph node involvement ( p  &lt; 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.</description><identifier>ISSN: 0171-5216</identifier><identifier>EISSN: 1432-1335</identifier><identifier>DOI: 10.1007/s00432-022-04336-z</identifier><identifier>PMID: 36063222</identifier><language>eng</language><publisher>Berlin/Heidelberg: Springer Berlin Heidelberg</publisher><subject>Amino acids ; Cancer Research ; Clinical significance ; Dehydrogenases ; Exons ; Hematology ; Histidine ; Immunohistochemistry ; Internal Medicine ; Isocitrate dehydrogenase ; Laryngeal cancer ; Laryngeal carcinoma ; Lymph nodes ; Malignancy ; Medicine ; Medicine &amp; Public Health ; Mutation ; Oncology ; Patients ; Polymerase chain reaction ; Squamous cell carcinoma ; Statistical analysis ; Tumor cells ; Tumors</subject><ispartof>Journal of cancer research and clinical oncology, 2023-07, Vol.149 (8), p.4253-4267</ispartof><rights>The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2022. 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The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c419t-d1837bcdb5b1aca7a61506a91d45570f9307ba0c835a5350f90438d97443c9683</citedby><cites>FETCH-LOGICAL-c419t-d1837bcdb5b1aca7a61506a91d45570f9307ba0c835a5350f90438d97443c9683</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,780,784,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/36063222$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Shayanfar, Nasrin</creatorcontrib><creatorcontrib>Zare-Mirzaie, Ali</creatorcontrib><creatorcontrib>Mohammadpour, Mahsa</creatorcontrib><creatorcontrib>Jafari, Ensieh</creatorcontrib><creatorcontrib>Mehrtash, Amirhosein</creatorcontrib><creatorcontrib>Emtiazi, Nikoo</creatorcontrib><creatorcontrib>Tajik, Fatemeh</creatorcontrib><title>Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma</title><title>Journal of cancer research and clinical oncology</title><addtitle>J Cancer Res Clin Oncol</addtitle><addtitle>J Cancer Res Clin Oncol</addtitle><description>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  &lt; 0.001), perineural invasion ( p  = 0.019), and lymph node involvement ( p  &lt; 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. 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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  &lt; 0.001), perineural invasion ( p  = 0.019), and lymph node involvement ( p  &lt; 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. 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subjects Amino acids
Cancer Research
Clinical significance
Dehydrogenases
Exons
Hematology
Histidine
Immunohistochemistry
Internal Medicine
Isocitrate dehydrogenase
Laryngeal cancer
Laryngeal carcinoma
Lymph nodes
Malignancy
Medicine
Medicine & Public Health
Mutation
Oncology
Patients
Polymerase chain reaction
Squamous cell carcinoma
Statistical analysis
Tumor cells
Tumors
title Low expression of isocitrate dehydrogenase 1 (IDH1) R132H is associated with advanced pathological features in laryngeal squamous cell carcinoma
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