MLH1 AND MSH2 PROTEIN EXPRESSION LOSS AND MICROSATELLITE INSTABILITY IN COLORECTAL ADENOMAS OF PATIENTS WITH LYNCH SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS Perda de expressão das proteínas MLH1 e MSH2 e instabilidade de microssatélites em adenomas colorretais de pacientes com Síndrome de Lynch: uma Revisão Sistemática e Meta-Análise
4 affiliations
- 1Federal University of Viçosa, Medicine and Nursing Department, Viçosa, MG, Brazil.
- 2Faculty Ciências Médicas de Minas Gerais, Medicine Department, Belo Horizonte, MG, Brazil.
- 3Gaziantep University, Faculty of Medicine, Şahinbey/Gaziantep, Turkey.
- 4Tunis El Manar University, Charles Nicolle Hospital, Research Laboratory in Immunology of Renal Transplantation and Immunopathology (LR03SP01), Tunisia.
Abstract
Background: : Lynch Syndrome (LS) is a genetic condition associated with a high risk of colorectal cancer, often linked to microsatellite instability (MSI), which is caused by defects in DNA mismatch repair (MMR) genes such as MLH1 and MSH2. Although MMR deficiency and MSI are well-documented in the literature, the role of these genes in adenomas remains unclear.
Objectives: : To evaluate, through meta-analysis, the correlation between loss of expression of the MLH1 and MSH2 genes and MSI in adenomas from patients with LS.
Methods: : A systematic search was conducted in the MEDLINE, SCOPUS, and Web of Science databases up to 06/09/2025, using a strategy with descriptors related to MSI, LS, and precursor lesions. Data were analyzed using the Inverse Variance method, with 95% confidence intervals. Heterogeneity was assessed using the I-squared ( I²) statistic. Outliers were identified through statistical influence diagnostics applied to each study. Publication bias was assessed using funnel plots and Egger’s regression test. Statistical analyses were performed using RStudio, version 4.4.0.
Results: : 5 studies were included, totaling 145 adenomas from individuals with LS. A highly significant correlation was found between MSI and MSH2 expression loss (OR=13,91 [3,97-48,72]; P=0,000038; I²=0%). No significant correlation was found between MSI and loss of MLH1 expression (OR=2,19 [0,93-5,16]; P=0,073; I²=0%). Funnel plot analysis and Egger’s regression test showed no significant evidence of publication bias for MLH1 (t=0.25, df=3, P-value=0.8155) or MSH2 (t=-0.79, df=3, P-value=0.4860).
Conclusion: : This meta-analysis found a strong, significant and consistent correlation between MSI and MSH2 expression loss in adenomas, but a non-significant association for MLH1 expression loss. The lack of statistical significance in Egger’s test for both genes should be interpreted with caution due to the small number of included studies (k=5). The limited literature available highlights the need for further, larger-scale research.
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BibTeX
@article{xavier2026mlh1,
title = {{MLH1 AND MSH2 PROTEIN EXPRESSION LOSS AND MICROSATELLITE INSTABILITY IN COLORECTAL ADENOMAS OF PATIENTS WITH LYNCH SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS Perda de expressão das proteínas MLH1 e MSH2 e instabilidade de microssatélites em adenomas colorretais de pacientes com Síndrome de Lynch: uma Revisão Sistemática e Meta-Análise}},
author = {Gustavo Carreira XAVIER and Lucas Araújo VAZ and Marina Cota CALDEIRA and Hacer TEKIN and Tarak DHAOUADI},
journal = {Arquivos de gastroenterologia},
year = {2026},
month = oct,
doi = {10.1590/s0004-2803.24612026-081},
url = {https://europepmc.org/article/PMC/PMC13722409},
note = {CC BY},
}
RIS
TY - JOUR
TI - MLH1 AND MSH2 PROTEIN EXPRESSION LOSS AND MICROSATELLITE INSTABILITY IN COLORECTAL ADENOMAS OF PATIENTS WITH LYNCH SYNDROME: A SYSTEMATIC REVIEW AND META-ANALYSIS Perda de expressão das proteínas MLH1 e MSH2 e instabilidade de microssatélites em adenomas colorretais de pacientes com Síndrome de Lynch: uma Revisão Sistemática e Meta-Análise
AU - Gustavo Carreira XAVIER
AU - Lucas Araújo VAZ
AU - Marina Cota CALDEIRA
AU - Hacer TEKIN
AU - Tarak DHAOUADI
PY - 2026
DA - 2026/10/30
JO - Arquivos de gastroenterologia
DO - 10.1590/s0004-2803.24612026-081
UR - https://europepmc.org/article/PMC/PMC13722409
AB - Background: : Lynch Syndrome (LS) is a genetic condition associated with a high risk of colorectal cancer, often linked to microsatellite instability (MSI), which is caused by defects in DNA mismatch repair (MMR) genes such as MLH1 and MSH2. Although MMR deficiency and MSI are well-documented in the literature, the role of these genes in adenomas remains unclear. Objectives: : To evaluate, through meta-analysis, the correlation between loss of expression of the MLH1 and MSH2 genes and MSI in adenomas from patients with LS. Methods: : A systematic search was conducted in the MEDLINE, SCOPUS, and Web of Science databases up to 06/09/2025, using a strategy with descriptors related to MSI, LS, and precursor lesions. Data were analyzed using the Inverse Variance method, with 95% confidence intervals. Heterogeneity was assessed using the I-squared ( I²) statistic. Outliers were identified through statistical influence diagnostics applied to each study. Publication bias was assessed using funnel plots and Egger’s regression test. Statistical analyses were performed using RStudio, version 4.4.0. Results: : 5 studies were included, totaling 145 adenomas from individuals with LS. A highly significant correlation was found between MSI and MSH2 expression loss (OR=13,91 [3,97-48,72]; P=0,000038; I²=0%). No significant correlation was found between MSI and loss of MLH1 expression (OR=2,19 [0,93-5,16]; P=0,073; I²=0%). Funnel plot analysis and Egger’s regression test showed no significant evidence of publication bias for MLH1 (t=0.25, df=3, P-value=0.8155) or MSH2 (t=-0.79, df=3, P-value=0.4860). Conclusion: : This meta-analysis found a strong, significant and consistent correlation between MSI and MSH2 expression loss in adenomas, but a non-significant association for MLH1 expression loss. The lack of statistical significance in Egger’s test for both genes should be interpreted with caution due to the small number of included studies (k=5). The limited literature available highlights the need for further, larger-scale research.
SN - 0004-2803
SN - 1678-4219
ER -