Department of Neurosurgery, Qilu Hospital, Cheeloo College of Medicine and Institute of Brain and Brain-Inspired Science, Shandong University, Jinan, China.
Shandong Key Laboratory of Brain Health and Function Remodeling, Jinan, China.
CNS Neurosci Ther. 2024 Oct;30(10):e70044. doi: 10.1111/cns.70044.
Some lower-grade gliomas (LGG) are difficult to distinguish morphologically from glial cell proliferation or inflammatory changes during surgery, leading to a high risk of incorrect diagnosis. It is crucial to differentiate between the two for making surgical decisions. We define these critical cases as "ultra early stage lower-grade gliomas (UES-LGG)".
We analyzed 11 out of 13 cases diagnosed with "gliosis" or "inflammatory changes" during surgery who tested positive for isocitrate dehydrogenase (IDH). Additionally, we conducted qRT-PCR detection on 35 samples diagnosed with LGG during surgery and analyzed their DNA content within an effective circulating threshold range to infer the critical value between UES-LGG and LGG. We conducted experiments using five standardized samples to infer the limited range of accurate detection of UES-LGG during surgery.
In the comparative analysis of 11 samples and 35 samples, it was found that while there was no significant difference in the average DNA detection concentration between the two groups (159.36 ± 83.3 ng/μL and 146.83 ± 122.43 ng/μL), there was a notable statistical variance in the detection threshold for positive mutations (31.78 ± 1.14 and 26.14 ± 2.69, respectively). This suggests that the IDH mutation rate may serve as an indicator for differentiation between the two groups. Subsequently, DNA was extracted from standardized IDH mutant samples and subjected to gradient dilution for detection purposes. The results indicated a consistent increase in detection threshold as detection concentration decreased. When the detection concentration fell below <0.1 ng/μL, it became impossible to carry out effective threshold range detections. To further identify the precise detection interval, we conducted gradient division once again and sought to simulate the functional relationship between DNA copy number and cycle threshold within this interval. The research revealed that when the minimum detection concentration exceeded 250 copies/μL, a 100% detection rate could be achieved.
This article defines UES-LGG as a tumor type easily misdiagnosed in clinical practice due to its extremely low positivity rate during surgery. The popularization of qRT-PCR based intraoperative molecular diagnosis greatly reduces errors caused by manual detection and improves disease detection rates during surgery. It provides a theoretical basis for more accurate surgical plans for surgeons.
在手术中，一些低级胶质瘤（LGG）在形态上很难与神经胶质细胞增生或炎症改变区分开来，导致误诊风险很高。因此，准确区分这两种情况对于手术决策至关重要。我们将这些难以鉴别的病例定义为“超早期 LGG（UES-LGG）”。
我们分析了 13 例在手术中被诊断为“胶质增生”或“炎症改变”且 IDH 阳性的病例，其中 11 例符合 UES-LGG 的定义。此外，我们对 35 例在手术中被诊断为 LGG 的病例进行了 qRT-PCR 检测，并分析了它们在有效循环阈值范围内的 DNA 含量，以推断 UES-LGG 和 LGG 之间的临界值。我们使用 5 个标准化样本进行了实验，以推断 UES-LGG 在手术中进行准确检测的有限范围。
在对 11 个样本和 35 个样本的比较分析中，发现两组之间的平均 DNA 检测浓度没有显著差异（159.36±83.3ng/μL 和 146.83±122.43ng/μL），但阳性突变的检测阈值存在显著的统计学差异（分别为 31.78±1.14 和 26.14±2.69）。这表明 IDH 突变率可能是两者之间的鉴别指标。随后，从标准化 IDH 突变样本中提取 DNA，并进行梯度稀释以进行检测。结果表明，随着检测浓度的降低，检测阈值呈一致增加趋势。当检测浓度低于<0.1ng/μL 时，无法进行有效的阈值范围检测。为了进一步确定精确的检测区间，我们再次进行梯度划分，并试图模拟该区间内 DNA 拷贝数与循环阈值之间的功能关系。研究表明，当最小检测浓度超过 250 拷贝/μL 时，可实现 100%的检测率。
本文将 UES-LGG 定义为一种在临床实践中由于其极低的阳性率而容易误诊的肿瘤类型。基于 qRT-PCR 的术中分子诊断的推广大大降低了手动检测带来的误差，提高了手术中的疾病检出率。它为外科医生制定更准确的手术计划提供了理论依据。
