全自动Idylla<sup>TM</sup>系统在中国结直肠癌微卫星不稳定性检测中的可行性研究

王乾; 张静; 郁成礼; 包龙龙; 蔡旭; 蒋文华; 黄丹; 盛伟琪; 朱晓丽; 周晓燕; 柏乾明

doi:10.19401/j.cnki.1007-3639.2022.11.006

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全自动Idylla^TM系统在中国结直肠癌微卫星不稳定性检测中的可行性研究

论著 | 更新时间：2025-12-31

- 全自动Idylla^TM系统在中国结直肠癌微卫星不稳定性检测中的可行性研究
- Validation of the fully automated Idylla^TM system for microsatellite instability detection in Chinese colorectal cancers
- 中国癌症杂志 2022年32卷第11期页码：1084-1090
- 作者机构：
  
  复旦大学附属肿瘤医院病理科，复旦大学上海医学院肿瘤学系，复旦大学病理研究所，上海 200032
- 作者简介：
  
  [ "王乾（ORCID: 0000-0001-6998-9740），硕士。" ]
  柏乾明（ORCID: 0000-0003-0657-9845），博士，副主任医师。
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2022.11.006
  中图分类号： R735.3+5;R735.3+7
- 收稿：2022-05-12，
  
  修回：2022-08-09，
  
  纸质出版：2022-11-30
- 稿件说明：
移动端阅览
王乾, 张静, 郁成礼, 等. 全自动Idylla^TM系统在中国结直肠癌微卫星不稳定性检测中的可行性研究[J]. 中国癌症杂志, 2022,32(11):1084-1090.

Qian WANG, Jing ZHANG, Chengli YU, et al. Validation of the fully automated Idylla^TM system for microsatellite instability detection in Chinese colorectal cancers[J]. China Oncology, 2022, 32(11): 1084-1090.
王乾, 张静, 郁成礼, 等. 全自动Idylla^TM系统在中国结直肠癌微卫星不稳定性检测中的可行性研究[J]. 中国癌症杂志, 2022,32(11):1084-1090. DOI： 10.19401/j.cnki.1007-3639.2022.11.006.

Qian WANG, Jing ZHANG, Chengli YU, et al. Validation of the fully automated Idylla^TM system for microsatellite instability detection in Chinese colorectal cancers[J]. China Oncology, 2022, 32(11): 1084-1090. DOI： 10.19401/j.cnki.1007-3639.2022.11.006.

摘要

背景与目的：

微卫星不稳定性（microsatellite instability，MSI）与错配修复（mismatch repair，MMR）基因缺陷，作为结直肠癌（colorectal cancer，CRC）等泛肿瘤免疫治疗的重要生物标志物之一，其检测近年来备受关注。目前临床上常用的多重荧光聚合酶链反应（polymerase chain reaction，PCR）检测MSI的传统方法（如Promega等），通常需要非肿瘤组织对照及较长的检测周期。Idylla

系统作为一种全自动定量PCR装置，检测MSI无需非肿瘤组织对照，且运行时间仅为2.5 h，具有较好的临床应用前景。但在国内临床应用前，应在中国CRC患者中验证该方法的可靠性。

方法：

收集2017年3月—2019年3月复旦大学附属肿瘤医院的87例CRC患者用40%甲醛溶液固定石蜡包埋（formalin-fixed paraffin-embedded，FFPE）的组织样本，分别采用免疫组织化学（immunochemistry，IHC）、传统PCR（Promega）和Idylla

3种方法进行MMR/MSI检测并比较分析，评估Idylla

系统临床检测的灵敏度和特异度以及在不同肿瘤含量样本中的可重复性。

结果：

87例CRC患者中，IHC和Promega的检测结果完全一致，其中56例被判定为MMR缺陷（deficient MMR，dMMR）/高度MSI（MSI-high，MSI-H），31例为MMR完整（proficient MMR，pMMR）/微卫星稳定（micro

satellite stable，MSS）。然而，其中4例dMMR/MSI-H患者被Idylla

MSI系统诊断为MSS，1例pMMR/MSS患者被诊断为MSI-H。若以IHC/Promega为参考标准，Idylla

MSI系统的诊断灵敏度为92.9%（52/56），特异度为96.8%（30/31），总体一致率达94.3%（82/87）。随后，应用Idylla

系统对上述不一致的5例患者进行重复检测，其中4例肿瘤含量≥20%的病例检测结果与IHC/Promega MSI检测一致，但1例肿瘤含量仅为5%的病例仍与IHC/Promega不一致，被误诊为MSS。最后，针对该病例，通过激光捕获显微切割技术对肿瘤细胞进行富集后，应用Idylla

MSI系统再次检测，结果显示为MSI-H。此外，选取5例具有不同肿瘤含量（20% ~ 60%）的病例，分别进行3次重复性验证，结果显示，Idylla

系统具有高度可重复性。

结论：

对于肿瘤含量≥20%的CRC患者，Idylla

系统可以为临床MSI检测提供一种快速、可靠、全自动的解决方案，并具有较高的灵敏度、特异度和可重复性。

Abstract

Background and purpose:

Microsatellite instability (MSI) and mismatch repair (MMR) defects have attracted much attention recently as one of the important biomarkers for pan-tumor immunotherapy such as colorectal cancer (CRC). Conventional methods for MSI detection with polymerase chain reaction (PCR) often require non-tumor controls as well as a long turnaround time. The Idylla

system as a fully automated quantitative PCR unit with a turnaround time of only 2.5 h should be proved for its reliability among Chinese CRC patients before application.

Methods:

Formalin-fixed paraffin-embedded (FFPE) tissue samples were collected from 87 CRC patients in Fudan University Shanghai Cancer Center from March 2017 to March 2019 and were subjected to detect MMR protein expression and MSI using immunochemistry (IHC)

conventional PCR (Promega MSI analysis) and the Idylla

MSI system

respectively.

Results:

Of the 87 CRC patients enrolled

56 cases were identified to be deficient MMR (dMMR)/MSI-high (MSI-H) and 31 to be proficient MMR (pMMR)/microsatellite stable (MSS) by both IHC and Promega MSI analysis. However

4 cases with dMMR/MSI-H were determined to be MSS and one case with pMMR/MSS to be MSI-H using Idylla

MSI system

yielding a sensitivity of 92.9% (52/56)

specificity of 96.8% (30/31) and an o

verall concordance of 94.3% (82/87). Then

the above five discordant cases were re-examined using Idylla

with resection tissues

as a result

four cases with ≥20% tumor contents changed to be consistent with IHC/Promega MSI assay

however

there was still one inconsistent case with only 5% tumor content. Subsequently

the case was reconfirmed using Idylla

with enriched tumor tissue by macrodissection

as expected

the result was demonstrated to be MSI-H

consistent with Promega MSI analysis and IHC. Furthermore

repeatability of the Idylla

MSI assay was proved to be reliable in 5 cases with various tumor contents (20%-60%).

Conclusion:

The Idylla

MSI system provides a fast

reliable and fully automated solution to MSI detection in Chinese CRC patients with high sensitivity

specificity and reproducibility

especially for CRC with more than 20% tumor contents.

关键词

Keywords

references

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Validation of the fully automated IdyllaTM system for microsatellite instability detection in Chinese colorectal cancers

DOI：10.19401/j.cnki.1007-3639.2022.11.006

摘要

Abstract

关键词

Keywords

references

全自动Idylla^TM系统在中国结直肠癌微卫星不稳定性检测中的可行性研究

Validation of the fully automated Idylla^TM system for microsatellite instability detection in Chinese colorectal cancers