Microsatellite instability as a possible diagnostic marker of the gastric mucosa dysplasia

Kononov AV, Rubtsov VA, Parygina MN, et al. . Microsatellite instability as a possible diagnostic marker of the gastric mucosa dysplasia. Russian Journal of Archive of Pathology. 2025;87(3):5‑16. (In Russ.)
https://doi.org/10.17116/patol2025870315

Подписка 2026 Архив патологии (Russian Journal of Archive of Pathology)

Использование инфографики авторами научных работ

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OBJECTIVE

To evaluate the MMR system proteins and the MSI status of regenerative (indefinite for dysplasia) and pronounced (epithelial dysplasia) gastric mucosa precancerous lesions in the comparison with cancer to determine their possible potential as a diagnostic markers of gastric mucosa dysplasia.

MATERIAL AND METHODS

The study included 2 groups of gastric mucosa specimens: (1) 150 biopsy gastric mucosa specimens: 43 with low-grade dysplasia, 32 with high-grade dysplasia, 75 — indefinite for dysplasia; (2) 155 cancer tissue specimens from resected stomachs. Gastric mucosa specimens were examined histologically, immunohistochemically using mouse monoclonal antibodies to the MMR system proteins: MLH-1, MSH2, MSH6, PMS2 (Diagnostic BioSystems, USA). MSI was studied with multiplex PCR evaluation of DNA microsatellites (NR-21, NR-24, NR-27, BAT-25, BAT-26) from paraffin sections, their analysis with capillary electrophoresis. The obtained data were processed with the Statistica 10.0 (StatSoft, USA), presented using descriptive, analytical statistics.

RESULTS

MSI was detected by immunohistochemistry in 8% (n=6) of the studied cases of low/high grade dysplasia, which does not have statistically significant differences from the distribution of MSI in the gastric cancer group (12% of microsatellite-unstable cases (n=18)) (p=0.49). MSI was not detected in any indefinite for dysplasia case.

CONCLUSION

Detection of microsatellite instability in gastric mucosa dysplasia indicates the likelihood of its occurrence at the early stages of the carcinogenesis cascade and makes it possible to use it to assess the risk of gastric cancer associated with microsatellite instability. The absence of instability in cases indefinite for dysplasia determines the possibility of its use for differential diagnosis of truly neoplastic and regenerative/reactive changes in the gastric mucosa.

Keywords:

gastric cancer

microsatellite instability

epithelial dysplasia

indefinite for dysplasia

cancer prevention

Authors:

Kononov A.V.

Omsk State Medical University

ORCID: 0000-0001-8607-7831

Rubtsov V.A.

Omsk State Medical University

ORCID: 0000-0003-1834-3629

Parygina M.N.

Omsk State Medical University

ORCID: 0000-0001-8006-3260

Demidova E.V.

«Vector-Best»

ORCID: 0009-0008-9957-5889

Mozgovoi S.I.

Omsk State Medical University

ORCID: 0000-0001-7200-7082

Pomorgailo E.G.

Omsk State Medical University

ORCID: 0000-0002-9857-1674

Shimanskaya A.G.

Omsk State Medical University

ORCID: 0000-0003-0949-8709

Markelova M.V.

Omsk State Medical University

ORCID: 0000-0002-5356-9669

Received:

29.11.2024

Accepted:

26.02.2025

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References:

Bray F, Laversanne M, Sung H, Ferlay J, Siegel RL, Soerjomataram I, Jemal A. Global cancer statistics 2022: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin. 2024;74(3):229-263. https://doi.org/10.3322/caac.21834
Kaprin AD, Starinskii VV, Shakhzadova AO, Lisichnikova IV, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2022 godu (zabolevaemost’ i smertnost’). Moscow: MNIOI im. P.A. Gertsena — filial FGBU «NMITs radiologii» Minzdrava Rossii; 2023. 275p. (In Russ.).
Kaprin AD, Starinskii VV, Shakhzadova AO, eds. Zlokachestvennye novoobrazovaniya v Rossii v 2023 godu (zabolevaemost’ i smertnost’). Moscow: MNIOI im. P.A. Gertsena − filial FGBU «NMITs radiologii» Minzdrava Rossii; 2024. 276p. (In Russ.).
Kaprin AD, Starinskii VV, Shakhzadova AO, eds. Sostoyanie onkologicheskoi pomoshchi naseleniyu Rossii v 2023 godu. Moscow: MNIOI im. P.A. Gertsena − filial FGBU «NMITs radiologii» Minzdrava Rossii; 2024. 262p. (In Russ.).
Shi D, Yang Z, Cai Y, Li H, Lin L, Wu D, Zhang S, Guo Q. Research advances in the molecular classification of gastric cancer. Cell Oncol (Dordr). 2024;47(5):1523-1536. https://doi.org/10.1007/s13402-024-00951-9
Zeng Y, Jin RU. Molecular pathogenesis, targeted therapies, and future perspectives for gastric cancer. Semin Cancer Biol. 2022;86(Pt. 3):566-582. https://doi.org/10.1016/j.semcancer.2021.12.004
Pretzsch E, Bösch F, Todorova R, Nieß H, Jacob S, Guba M, Kirchner T, Werner J, Klauschen F, Angele MK, et al. Molecular subtyping of gastric cancer according to ACRG using immunohistochemistry — correlation with clinical parameters. Pathol Res Pract. 2022;231:153797. https://doi.org/10.1016/j.prp.2022.153797
Danilova NV, Chaika AV, Khomyakov VM, Oleinikova NA, Andreeva YuYu, Mal’kov PG. Microsatellite instability in gastric cancer is a predictor of a favorable prognosis. Russian Journal of Archive of Pathology. 2022;84(6):5-15. (In Russ.). https://doi.org/10.17116/patol2022840615
Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, Liu J, Yue YG, Wang J, Yu K, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449-456. https://doi.org/10.1038/nm.3850
Fassan M, Simbolo M, Bria E, Mafficini A, Pilotto S, Capelli P, Bencivenga M, Pecori S, Luchini C, Neves D, et al. High-throughput mutation profiling identifies novel molecular dysregulation in high-grade intraepithelial neoplasia and early gastric cancers. Gastric Cancer. 2014;17(3):442-449. https://doi.org/10.1007/s10120-013-0315-1
Guan WL, He Y, Xu RH. Gastric cancer treatment: recent progress and future perspectives. J Hematol Oncol. 2023;16(1):57. https://doi.org/10.1186/s13045-023-01451-3
Joshi SS, Badgwell BD. Current treatment and recent progress in gastric cancer. CA Cancer J Clin. 2021;71(3):264-279. https://doi.org/10.3322/caac.21657
Li F, Wang Y, Ping X, Yin JC, Wang F, Zhang X, Li X, Zhai J, Shen L. Molecular evolution of intestinal-type early gastric cancer according to Correa cascade. J Biomed Res. 2024;38:1-8. https://doi.org/10.7555/JBR.38.20240118
Min BH, Hwang J, Kim NK, Park G, Kang SY, Ahn S, Ahn S, Ha SY, Lee YK, Kushima R, et al. Dysregulated Wnt signalling and recurrent mutations of the tumor suppressor RNF43 in early gastric carcinogenesis. J Pathol. 2016;240(3):304-314. https://doi.org/10.1002/path.4777
Garay J, Bravo JC, Correa P, Schneider BG. Infrequency of microsatellite instability in complete and incomplete gastric intestinal metaplasia. Hum Pathol. 2004;35(1):102-106. https://doi.org/10.1016/j.humpath.2003.08.023
Li B, Liu HY, Guo SH, Sun P, Gong FM, Jia BQ. Microsatellite instability of gastric cancer and precancerous lesions. Int J Clin Exp Med. 2015;8(11):21138-21144.
Han X, Jiang K, Wang B, Zhou L, Chen X, Li S. Effect of rebamipide on the premalignant progression of chronic gastritis: a randomized controlled study. Clin Drug Investig. 2015;35(10):665-673. https://doi.org/10.1007/s40261-015-0329-z
Kononov AV, Mozgovoi SI, Shimanskaya AG, Markelova MV, Osintseva IL, Vas’kina TV, Panyushkin LV. Rossiiskii peresmotr klassifikatsii khronicheskogo gastrita: vosproizvodimost’ otsenki patomorfologicheskoi kartiny. Russian Journal of Archive of Pathology. 2011;73(4):52-56. (In Russ.).
The WHO Classification of Tumours Editorial Board. WHO Classification of Tumours. Digestive system tumours. 5th ed. Vol. 1. Lyon, France: IARC; 2019.
Kononov AV, Mozgovoi SI, Shimanskaya AG. Prizhiznennaya patologo-anatomicheskaya diagnostika boleznei organov pishchevaritel’noi sistemy (klass XI MKB-10). Klinicheskie rekomendatsii. Moscow: Prakticheskaya meditsina; 2019. (In Russ.).
Mozgovoi SI. Algoritm opredeleniya tipa kishechnoi metaplazii slizistoi obolochki zheludka s pomoshch’yu kombinirovannykh gistokhimicheskikh metodov. Arkhiv Patologii. 2009;71(4): 46-47. (In Russ.)
Koo M, Squires JM, Ying D, Huang J. Making a tissue microarray. Methods Mol Biol. 2019;1897:313-323. https://doi.org/10.1007/978-1-4939-8935-5_27
Patel PG, Selvarajah S, Boursalie S, How NE, Ejdelman J, Guerard KP, Bartlett JM, Lapointe J, Park PC, Okello JB, et al. Preparation of formalin-fixed paraffin-embedded tissue cores for both RNA and DNA extraction. J Vis Exp. 2016;114:54299. https://doi.org/10.3791/54299
Cancer Genome Atlas Research Network. Comprehensive molecular characterization of gastric adenocarcinoma. Nature. 2014; 513(7517):202-209. https://doi.org/10.1038/nature13480
Cristescu R, Lee J, Nebozhyn M, Kim KM, Ting JC, Wong SS, Liu J, Yue YG, Wang J, Yu K, et al. Molecular analysis of gastric cancer identifies subtypes associated with distinct clinical outcomes. Nat Med. 2015;21(5):449-456. https://doi.org/10.1038/nm.3850
Mathiak M, Warneke VS, Behrens HM, Haag J, Böger C, Krüger S, Röcken C. Clinicopathologic characteristics of microsatellite instable gastric carcinomas revisited: urgent need for standardization. Appl Immunohistochem Mol Morphol. 2017;25(1):12-24. https://doi.org/10.1097/PAI.0000000000000264
Zhang Z, Huang J, Li Y, Yan H, Xie J, Wang J, Zhao B. Global burden, risk factors, clinicopathological characteristics, molecular biomarkers and outcomes of microsatellite instability-high gastric cancer. Aging (Albany NY). 2024;16(1):948-963. https://doi.org/10.18632/aging.205431
Polom K, Marano L, Marrelli D, De Luca R, Roviello G, Savelli V, Tan P, Roviello F. Meta-analysis of microsatellite instability in relation to clinicopathological characteristics and overall survival in gastric cancer. Br J Surg. 2018;105(3):159-167. https://doi.org/10.1002/bjs.10663
Yamamoto G, Ito T, Suzuki O, Kamae N, Kakuta M, Takahashi A, Iuchi K, Arai T, Ishida H, Akagi K. Concordance between microsatellite instability testing and immunohistochemistry for mismatch repair proteins and efficient screening of mismatch repair deficient gastric cancer. Oncol Lett. 2023;26(5):494. https://doi.org/10.3892/ol.2023.14081
Guyot D’Asnières De Salins A, Tachon G, Cohen R, Karayan-Tapon L, Junca A, Frouin E, Godet J, Evrard C, Randrian V, Duval A, et al. Discordance between immunochemistry of mismatch repair proteins and molecular testing of microsatellite instability in colorectal cancer. ESMO Open. 2021;6(3):100120. https://doi.org/10.1016/j.esmoop.2021.100120