P53 杂合性缺失（LOH）在福尔马林固定石蜡包埋平滑肌肉瘤（LMS）中的检测：一项新的报告。
P53 loss of heterozygosity (LOH) in formalin-fixed paraffin-embedded leiomyosarcoma (LMS): a novel report.
机构信息
Research Laboratory, St Vincent's University Hospital, University College Dublin, PathologyDublin, Ireland.
Department of Histopathology, St James's Hospital and Trinity College Dublin, Dublin, Ireland.
出版信息
Ir J Med Sci. 2024 Feb;193(1):65-71. doi: 10.1007/s11845-023-03370-1. Epub 2023 Jul 20.
BACKGROUND
The occurrence of p53 loss of heterozygosity (LOH) is a common genetic event in malignancy. LOH occurs when a heterozygous locus loses one of its two parental alleles, becoming homozygous at that locus, by either copy number loss (CNL-LOH) or by becoming copy number neutral (CNN-LOH). A role for CNL-LOH (cnLOH) has been postulated in cancer aetiology. Loss of heterozygosity (LOH) results in irreversible genetic loss.
AIMS
LOH was determined in DNA extracted from formalin-fixed paraffin-embedded (FFPE) leiomyosarcoma (LMS) specimens in a retrospective study from 30 patients, to assess the prognostic significance of LOH. The findings were analysed and their validity assessed. LOH was an adverse prognostic factor in LMS. Prospective uniform standardisation of formalin-fixation techniques is required.
METHODS
DNA was extracted from 169 formalin-fixed paraffin blocks of 30 patients with LMS, following extensive tissue microdissection. Genomic DNA was amplified using the polymerase chain reaction (PCR) technique. Fluorescence-based microsatellite PCR was used to detect and quantitate heterozygosity loss.
RESULTS
LOH was detected at gene locus 17p13 in 16 LMS (Four grade 2 and 12 grade 3 LMS). LOH was not detected in 14 LMS cases (one grade 1, five grade 2 and eight grade 3 LMS). LOH was associated with shorter patient survival.
CONCLUSIONS
The results reported herein endorse the value of utilizing FFPE DNA in identifying LOH as a prognostic factor in LMS. The results have implications for tumour biobanking and precision medicine in patients with sarcomas.
背景
p53 杂合性丢失（LOH）的发生是恶性肿瘤中常见的遗传事件。杂合子位点失去其两个亲本等位基因之一，成为该位点的纯合子，通过拷贝数丢失（CNL-LOH）或成为拷贝数中性（CNN-LOH）。已经提出了 CNL-LOH（cnLOH）在癌症发病机制中的作用。LOH 导致不可逆转的遗传丢失。
目的
在一项来自 30 名患者的回顾性研究中，从福尔马林固定石蜡包埋（FFPE）平滑肌肉瘤（LMS）标本中提取 DNA，确定 LOH，以评估 LOH 的预后意义。分析了这些发现并评估了其有效性。LOH 是 LMS 的不良预后因素。需要对福尔马林固定技术进行前瞻性统一标准化。
方法
对 30 名 LMS 患者的 169 个福尔马林固定石蜡块进行组织微切割后，从 169 个福尔马林固定石蜡块中提取 DNA。使用聚合酶链反应（PCR）技术扩增基因组 DNA。荧光微卫星 PCR 用于检测和定量杂合性丢失。
结果
在 16 例 LMS 中（4 级 2 例，12 级 3 例）检测到 17p13 基因座的 LOH。在 14 例 LMS 病例中未检测到 LOH（1 级 1 例，2 级 5 例，3 级 8 例）。LOH 与患者生存时间缩短相关。
结论
本文报告的结果支持在 LMS 中利用 FFPE DNA 鉴定 LOH 作为预后因素的价值。这些结果对肉瘤患者的肿瘤生物库和精准医学具有重要意义。
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