结肠直肠癌错配修复蛋白表达与微卫星稳定性的一致性分析
收稿日期: 2024-02-24
网络出版日期: 2024-07-01
Consistency analysis of mismatch repair protein expression and microsatellite stability in colorectal cancer
Received date: 2024-02-24
Online published: 2024-07-01
目的：探究免疫组织化学(IHC)检测错配修复(MMR)状态与二代测序(NGS)鉴定的微卫星不稳定性(MSI)的一致性，并评估其结果与中国结肠直肠癌（CRC）病人临床特征的相关性。方法：采用IHC和NGS测序分别鉴定CRC的MMR及MSI状态，评估不同检测方式的一致性。结果：IHC与NGS检测方式一致性为98.36%，一致性良好（Kappa=0.856）。pMMR/MSI-H亚型中存在一定的致病性或可能致病性胚系变异，dMMR/MSS亚型中MLH1和PMS2共同缺失最为常见。分型不一致的病人多集中于发病较早的右半结肠（P<0.01），且分化相对较差。结论：经IHC和NGS检测的MSI一致性很好，可高达98%以上。为避免因MSI状态误诊而影响临床医师对治疗方案的决策，对于分化较差的早期阶段右半结肠必须高度重视MSI分析的准确性。
朱惠, 蔡继东, 李溟涵, 杨文涛, 徐烨 . 结肠直肠癌错配修复蛋白表达与微卫星稳定性的一致性分析[J]. 外科理论与实践, 2024 , 29(02) : 148 -155 . DOI: 10.16139/j.1007-9610.2024.02.10
Objective To investigate the consistency between mismatch repair proyeins expressions detected by immunohistochemistry (IHC) and microsatellite instability(MSI) identified by next-generation sequencing (NGS), and evaluate the correlation of these results with the clinical characteristics of Chinese colorectal cancer (CRC). Methods Using IHC and NGS to identify mismatch repair (MMR) and MSI status in CRC, and assessing the consistency between these different detection methods. Results The concordance rate of MSI status detected by IHC and NGS was 98.36%, indicating good agreement (Kappa=0.856). Certain pathogenic or likely pathogenic germline variants were present in the pMMR/MSI-H subtype. The co-deficiency of MLH1 and PMS2 was most common in the dMMR/MSS subtype. Patients with inconsistent typing were more likely to have early-onset right-sided colon cancer (P<0.01) and the tumor with relatively poor differentiation. Conclusions The consistency of MSI status detected by IHC and NGS is very high, 98% or more. To avoid the misdiagnosis of MSI status affecting clinical decision-making for treatment plans, it is imperative to ensure the accuracy of MSI analysis, particularly in poorly differentiated early-stage right-sided colon cancers.
| [1] | SUNG H, FERLAY J, SIEGEL R L, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries[J]. CA Cancer J Clin, 2021, 71(3):209-249. |
| [2] | SIEGEL R L, MILLER K D, WAGLE N S, et al. Cancer statistics, 2023[J]. CA Cancer J Clin, 2023, 73(1):17-48. |
| [3] | ZHANG Y, CHEN Z, LI J. The current status of treatment for colorectal cancer in China: a systematic review[J]. Medicine (Baltimore), 2017, 96(40):e8242. |
| [4] | LOUGHREY M B, MCGRATH J, COLEMAN H G, et al. Identifying mismatch repair-deficient colon cancer: near-perfect concordance between immunohistochemistry and microsatellite instability testing in a large, population-based series[J]. Histopathology, 2021, 78(3):401-413. |
| [5] | LATHAM A, SRINIVASAN P, KEMEL Y, et al. Microsatellite instability is associated with the presence of lynch syndrome pan-cancer[J]. J Clin Oncol, 2019, 37(4): 286-295. |
| [6] | YAMAMOTO H, IMAI K. Microsatellite instability: an update[J]. Arch Toxicol, 2015, 89(6):899-921. |
| [7] | CHUNG J, MARUVKA Y E, SUDHAMAN S, et al. DNA polymerase and mismatch repair exert distinct microsatellite instability signatures in normal and malignant human cells[J]. Cancer Discov, 2021, 11(5):1176-1191. |
| [8] | YE M, RU G, YUAN H, et al. Concordance between microsatellite instability and mismatch repair protein expression in colorectal cancer and their clinicopathological characteristics: a retrospective analysis of 502 cases[J]. Front Oncol, 2023,13:1178772. |
| [9] | CHEN J, YAN Q, SUN J, et al. Microsatellite status detection of colorectal cancer: evaluation of inconsistency between PCR and IHC[J]. J Cancer, 2023, 14(7):1132-1140. |
| [10] | MIDDHA S, ZHANG L, NAFA K, et al. Reliable pan-cancer microsatellite instability assessment by using targeted next-generation sequencing data[J]. JCO Precis Oncol, 2017,2017:PO.17.00084. |
| [11] | NIU B, YE K, ZHANG Q, et al. MSIsensor: microsatellite instability detection using paired tumor-normal sequence data[J]. Bioinformatics, 2014, 30(7):1015-1016. |
| [12] | LE D T, DURHAM J N, SMITH K N, et al. Mismatch repair deficiency predicts response of solid tumors to PD-1 blockade[J]. Science, 2017, 357(6349):409-413. |
| [13] | DIAO Z, HAN Y, CHEN Y, et al. The clinical utility of microsatellite instability in colorectal cancer[J]. Crit Rev Oncol Hematol, 2021,157:103171. |
| [14] | MARABELLE A, LE D T, ASCIERTO P A, et al. Efficacy of pembrolizumab in patients with noncolorectal high microsatellite instability/mismatch repair-deficient cancer: results from the phase Ⅱ KEYNOTE-158 study[J]. J Clin Oncol, 2020, 38(1):1-10. |
| [15] | KAWAKAMI H, ZAANAN A, SINICROPE F A. Microsatellite instability testing and its role in the management of colorectal cancer[J]. Curr Treat Options Oncol, 2015, 16(7):30. |
| [16] | LAU D K, BURGE M, ROY A, et al. Update on optimal treatment for metastatic colorectal cancer from the AGITG expert meeting: ESMO congress 2019[J]. Expert Rev Anticancer Ther, 2020, 20(4):251-270. |
| [17] | MARCUS L, LEMERY S J, KEEGAN P, et al. FDA approval summary: pembrolizumab for the treatment of microsatellite instability-high solid tumors[J]. Clin Cancer Res, 2019, 25(13):3753-3758. |
| [18] | SARGENT D J, MARSONI S, MONGES G, et al. Defective mismatch repair as a predictive marker for lack of efficacy of fluorouracil-based adjuvant therapy in colon cancer[J]. J Clin Oncol, 2010, 28(20):3219-3226. |
| [19] | COHEN R, HAIN E, BUHARD O, et al. Association of primary resistance to immune checkpoint inhibitors in metastatic colorectal cancer with misdiagnosis of microsatellite instability or mismatch repair deficiency status[J]. JAMA Oncol, 2019, 5(4):551-555. |
| [20] | YOSHINO T, PENTHEROUDAKIS G, MISHIMA S, et al. JSCO-ESMO-ASCO-JSMO-TOS: international expert consensus recommendations for tumour-agnostic treatments in patients with solid tumours with microsatellite instability or NTRK fusions[J]. Ann Oncol, 2020, 31(7):861-872. |
| [21] | DEDEURWAERDERE F, CLAES K B, VAN DORPE J, et al. Comparison of microsatellite instability detection by immunohistochemistry and molecular techniques in colorectal and endometrial cancer[J]. Sci Rep, 2021, 11(1):12880. |
| [22] | ADAM R, SPIER I, ZHAO B, et al. Exome sequencing identifies biallelic MSH3 germline mutations as a recessive subtype of colorectal adenomatous polyposis[J]. Am J Hum Genet, 2016, 99(2):337-351. |
| [23] | EVRARD C, TACHON G, RANDRIAN V, et al. Microsatellite instability: diagnosis, heterogeneity, discordance, and clinical impact in colorectal cancer[J]. Cancers (Basel), 2019, 11(10):1567. |
| [24] | LI G M. Mechanisms and functions of DNA mismatch repair[J]. Cell Res, 2008, 18(1):85-98. |
| [25] | BAI H, WANG R, CHENG W, et al. Evaluation of concordance between deficient mismatch repair and microsatellite instability testing and their association with clinicopathological features in colorectal cancer[J]. Cancer Manag Res, 2020,12:2863-2873. |
| [26] | CHEAH P L, LI J, LOOI L M, et al. Screening for microsatellite instability in colorectal carcinoma: practical utility of immunohistochemistry and PCR with fragment analysis in a diagnostic histopathology setting[J]. Malays J Pathol, 2019, 41(2):91-100. |
| [27] | LUCHINI C, BIBEAU F, LIGTENBERG M J L, et al. ESMO recommendations on microsatellite instability tes-ting for immunotherapy in cancer, and its relationship with PD-1/PD-L1 expression and tumour mutational burden: a systematic review-based approach[J]. Ann Oncol, 2019, 30(8):1232-1243. |
| [28] | SALAHSHOR S, KOELBLE K, RUBIO C, et al. Microsatellite instability and hMLH1 and hMSH2 expression analysis in familial and sporadic colorectal cancer[J]. Lab Invest, 2001, 81(4):535-541. |
| [29] | WANG C, KUANG W, ZENG J, et al. A retrospective study of consistency between immunohistochemistry and polymerase chain reaction of microsatellite instability in endometrial cancer[J]. PeerJ, 2023,11:e15920. |
/
| 〈 |
|
〉 |
