Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 29;19(1):155.
doi: 10.1186/s13000-024-01571-5.

Concordance between immunohistochemistry and MSI analysis for detection of MMR/MSI status in colorectal cancer patients

Muhammad Ishaque Faizee  1 , NorLelawati A Talib  2 , Asmah Hanim Bt Hamdan  2 , Nor Zamzila Bt Abdullah  2 , Bilal Ahmad Rahimi  3 , Ahmed Maseh Haidary  4 , Ramin Saadaat  5 , Ahmed Nasir Hanifi  6
Affiliations

Concordance between immunohistochemistry and MSI analysis for detection of MMR/MSI status in colorectal cancer patients

Muhammad Ishaque Faizee et al. Diagn Pathol. .

Abstract

Background: Recently, screening of colorectal cancer (CRC) patients for mismatch repair/microsatellite instability (MMR/MSI) status is widely practiced due to its potential predictive and prognostic roles and a screening tool to reveal Lynch Syndrome (LS). The purpose of the study was to evaluate concordance between immunohistochemistry (IHC) and MSI analysis methods for detection of MMR/MSI status in colorectal cancer patients in Kuantan, Pahang.

Methods: Fifty selected CRC cases of deficient mismatch repair (dMMR) and proficient mismatch repair (pMMR) which were identified immunohistochemically in the previous study were subjected to MSI analysis. MSI Analysis System 1.2 (Promega) was utilized.

Results: The results of MSI analysis method showed MSI-High: 26% (13/50), MSI-Low: 6% (3/50), and Microsatellite Stable: 68% (34/50). The concordance was perfect (0.896, Kappa value) between MSI analysis and IHC methods for the assessment of MMR/MSI status in CRC patients. The discordance was only 4% (2/50). MSI analysis identified all dMMR cases determined by IHC except one case. The obtained frequency of dMMR and pMMR patients was 11.4% (14/123) and 88.6% (109/123) by IHC method, respectively.

Conclusion: Our findings support the universal practice of evaluating the MMR/MSI status in all newly diagnosed CRC patients. Based on the perfect concordance of two methods, the method of choice is based on the availability of expertise and equipments. IHC is highly appreciable method due to its feasibility and reproducibility.

Keywords: Colorectal cancer; IHC; MMR; MSI; MSI analysis.

PubMed Disclaimer

Conflict of interest statement

Declarations. Ethical approval: All methods were carried out in accordance with relevant guidelines and regulations from National Medical Research Register (NMRR) of Malaysia and IIUM Research Ethic Committee (IREC); [NMRR-18-3675-45439(IIR)] and (IREC 2019 − 180), respectively. Since the research was conducted on FFPE blocks and no personal information is disclosed and the subjects are not identified, thus, no informed consent was taken from patients, a waiver of informed was obtained from International Islamic University Malaysia (IIUM). Consent for publication: Not applicable. Competing interests: The authors declare no competing interests.

Figures

Fig. 1
Fig. 1
IHC staining for PMS2 protein re-classified from dMMR to pMMR due to heterogenous staining
Fig. 2
Fig. 2
The loss of different MMR Proteins by IHC
Fig. 3
Fig. 3
Representative electropherograms of the positive MSI markers; (a) represents normal (lower) and corresponding tumour (upper) tissues with their alleles (prominent peaks) at Bat-25 locus; (b) represents normal (lower) and corresponding tumour (upper) tissues with their alleles (prominent peaks) at Bat-26 locus. The tumour tissues exhibited extra alleles not present in normal tissues
Fig. 4
Fig. 4
Representative electropherograms of the positive MSI markers; (c) represents normal (lower) and corresponding tumour (upper) tissues with their alleles (prominent peaks) at NR-21 locus; (d) represents normal (lower) and corresponding tumour (upper) tissues with their alleles prominent peaks) at NR-24 locus. The tumour tissues exhibited extra alleles not present in normal tissues
Fig. 5
Fig. 5
Representative electropherograms of the positive MSI markers; (e) represents normal (lower) and corresponding tumour (upper) tissues with their alleles (prominent peaks) at MONO-27 locus. The tumour tissue exhibited extra alleles not present in normal tissue
Fig. 6
Fig. 6
Individual distribution of unstable mononucleotide markers found in MSI positive CRC cases
Fig. 7
Fig. 7
MSI positive markers grouping distribution. n = 3 showed five marker positivity (NR-24, Bat-25, Bat-26, MONO-27, and NR-21); there are 2, 2, and 3 different marker combinations in cases with 4, 3, and 2 markers positivity, respectively
Fig. 8
Fig. 8
MSI-positive cases with MSI-H/MSI-L and pMMR/dMMR status
See this image and copyright information in PMC

References

    1. Nojadeh JN, Sharif SB. Sakhinia EJEj. Microsatellite Instability Colorectal cancer. 2018;17:159. - PMC - PubMed
    1. Diao Z, Han Y, Chen Y, Zhang R, Li J. The clinical utility of microsatellite instability in colorectal cancer. Crit Rev Oncol Hematol. 2021 Jan;157:103171. 10.1016/j.critrevonc.2020.103171. Epub 2020 Nov 25. PMID: 33290824. - PubMed
    1. Baretti M, Le DTJP, editors. therapeutics. DNA mismatch repair in cancer. 2018;189:45–62. - PubMed
    1. Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, Kwint MP, Hoogerbrugge N, Nagtegaal ID, Ligtenberg MJ. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology. 2014 Mar;146(3):643–46.e8. 10.1053/j.gastro.2013.12.002. Epub 2013 Dec 10. PMID: 24333619. - PubMed
    1. Mensenkamp AR, Vogelaar IP, van Zelst-Stams WA, Goossens M, Ouchene H, Hendriks-Cornelissen SJ, Kwint MP, Hoogerbrugge N, Nagtegaal ID, Ligtenberg MJ. Somatic mutations in MLH1 and MSH2 are a frequent cause of mismatch-repair deficiency in Lynch syndrome-like tumors. Gastroenterology. 2014 Mar;146(3):643–46.e8. 10.1053/j.gastro.2013.12.002. Epub 2013 Dec 10. PMID: 24333619. - PubMed

MeSH terms

Substances

LinkOut - more resources