Department of Pathology, Rasoul Akram Hospital, Iran University of Medical Sciences, Tehran, Iran.
Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
J Cancer Res Clin Oncol. 2023 Jul;149(8):4253-4267. doi: 10.1007/s00432-022-04336-z. Epub 2022 Sep 5.
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).
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).
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.
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.
近年来，基因组测序的发展使得人们在各种恶性肿瘤中发现了异柠檬酸脱氢酶 1（IDH1）的体细胞突变。IDH1 R132H 是 IDH1 最常见的突变，影响密码子 132，导致精氨酸（R）突变为组氨酸（H）。本研究旨在评估 IDH1 R132H 的表达与喉鳞状细胞癌（LSCC）的临床病理特征之间的关系。
采用免疫组织化学法检测 50 例 LSCC 肿瘤及相应癌旁组织的组织微阵列（TMA）中 IDH1 R132H 的表达模式及临床意义。然后对 12 例染色阴性/弱阳性的肿瘤样本进行聚合酶链反应（PCR）测序。
结果表明，肿瘤细胞中 IDH1 R132H 的细胞质表达较癌旁组织下调。IDH1 R132H 蛋白细胞质表达水平低与组织学分级增加（p<0.001）、神经周围侵犯（p=0.019）和淋巴结受累（p<0.001）显著相关。exon4 测序结果显示，仅 1 例样本 IDH1 R132H 突变阳性。39 例（78.0%）LSCC 样本中观察到 IDH1 R132H 表达。
这些发现表明，IDH1 R132H 细胞质表达水平降低可能对 LSCC 患者具有临床意义，并与肿瘤侵袭性更强、疾病进展有关，有助于改善 LSCC 患者的潜在治疗效果。需要进一步研究以了解 IDH1 R132H 的生物学功能，并需要更大的样本量来验证我们的研究结果。
