Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study
Abstract
1. Introduction
Objective
2. Material and Methods
2.1. Ethical or Institutional Review Board Approval
2.2. Study Design
2.3. Setting
2.4. Participants
2.5. Variables
2.6. Laboratory
2.7. Statistic Analysis
2.8. Risk of Bias
3. Results
3.1. Population Characteristics
3.2. Outcome
3.3. Sub-Analysis for Heterodimer
3.4. Logit Regression
4. Discussion
4.1. Interpretation of Results
4.2. Clinical Implications
4.3. Comparison with the Literature
4.4. Strenght and Limitations
4.5. Future Prospectives
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
BMI | Body Mass Index |
BIC | Bayesian Information Criterion |
CI | Confidence Interval |
EC | Endometrial Carcinoma |
FST | Fertility-Sparing Treatment |
IHC | Immunohistochemistry |
IRB | Institutional Review Board |
LVSI | Lymphovascular Space Invasion |
MLH1 | MutL Homolog 1 |
MMR | Mismatch Repair |
MMRd | Mismatch Repair deficient |
MMRp | Mismatch Repair proficient |
MRI | Magnetic Resonance Imaging |
MSH2 | MutS Homolog 2 |
MSH6 | MutS Homolog 6 |
MSI | Microsatellite Instability |
MSS | Microsatellite Stability |
OR | Odds Ratio |
PMS2 | Post-Meiotic Segregation Increased 2 |
ProMisE | Proactive Molecular Risk Classifier for Endometrial Cancer |
SLN | Sentinel Lymph Node |
TCGA | The Cancer Genome Atlas |
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Characteristic | MSI, N = 26 1 | MSS, N = 118 1 | p-Value 2 |
---|---|---|---|
Age | 66 (60, 76) | 62 (56, 71) | 0.066 |
BMI | 29 (27, 33) | 29 (25, 33) | 0.979 |
Missing | 0 | 1 | |
Ethnicity | >0.999 | ||
Caucasian | 26 (100%) | 116 (98%) | |
Hispanic | 0 (0%) | 1 (0.8%) | |
Indian | 0 (0%) | 1 (0.8%) | |
Grading | 0.002 | ||
1 | 5 (19%) | 62 (53%) | |
2 | 21 (81%) | 56 (47%) | |
LVSI | >0.999 | ||
Negative | 21 (81%) | 96 (82%) | |
Diffuse | 3 (12%) | 13 (11%) | |
Focal | 2 (7.7%) | 8 (6.8%) | |
Missing | 0 | 1 | |
Dimension | 20 (14, 25) | 20 (10, 30) | 0.879 |
Missing | 13 | 77 | |
Lymph Node Retrieved | 2.00 (2.00, 4.75) | 2.00 (2.00, 4.00) | 0.599 |
Characteristic | Intact Nuclear Expression, N = 118 1 | Loss of Both Heterodimers, N = 2 1 | Loss of MLH1/PMS2, N = 17 1 | Loss of MSH2/MSH6, N = 7 1 | p-Value 2 |
---|---|---|---|---|---|
Age | 62 (56, 71) | 70 (65, 74) | 66 (59, 76) | 68 (62, 71) | |
BMI | 29 (25, 33) | 32 (30, 34) | 28 (26, 31) | 33 (29, 35) | |
Missing | 1 | 0 | 0 | 0 | |
Ethnicity | >0.999 | ||||
Caucasian | 116 (98%) | 2 (100%) | 17 (100%) | 7 (100%) | |
Hispanic | 1 (0.8%) | 0 (0%) | 0 (0%) | 0 (0%) | |
Indian | 1 (0.8%) | 0 (0%) | 0 (0%) | 0 (0%) | |
Grading | 0.004 | ||||
1 | 62 (53%) | 1 (50%) | 2 (12%) | 2 (29%) | |
2 | 56 (47%) | 1 (50%) | 15 (88%) | 5 (71%) | |
LVSI | 0.822 | ||||
Negative | 96 (82%) | 2 (100%) | 14 (82%) | 5 (71%) | |
Focal | 8 (6.8%) | 0 (0%) | 1 (5.9%) | 1 (14%) | |
Diffuse | 13 (11%) | 0 (0%) | 2 (12%) | 1 (14%) | |
Missing | 1 | 0 | 0 | 0 | |
Dimension | 20 (10, 30) | NA (NA, NA) | 20 (15, 25) | 30 (22, 37) | |
Missing | 77 | 2 | 6 | 5 | |
Lymph Nodes Retrieved | 2.00 (2.00, 4.00) | 2.00 (2.00, 2.00) | 3.00 (2.00, 5.00) | 2.00 (2.00, 2.50) |
Characteristic | MSI, N = 26 1 | MSS, N = 118 1 | p-Value 2 |
---|---|---|---|
Myometrial Infiltration | 0.5 | ||
No Infiltration | 1, (3.8%) | 2, (1.7%) | |
Infiltration | 25, (96%) | 116, (98%) | |
Type of Infiltration | 0.042 | ||
No Infiltration | 1, (3.8%) | 2, (1.7%) | |
<50% | 15, (58%) | 94, (80%) | |
≥50% | 10, (38%) | 22, (19%) |
Characteristic. | Intact Nuclear Expression, N = 118 1 | Loss of Both Heterodimers, N = 2 1 | Loss of MLH1/PMS2, N = 17 1 | Loss of MSH2/MSH6, N = 7 1 | p-Value 2 |
---|---|---|---|---|---|
Myometrial Infiltration | 0.212 | ||||
No Infiltration | 2 (1.7%) | 0 (0%) | 0 (0%) | 1 (14%) | |
Infiltration | 116 (98%) | 2 (100%) | 17 (100%) | 6 (86%) | |
Type of Infiltration | 0.036 | ||||
No Infiltration | 2 (1.7%) | 0 (0%) | 0 (0%) | 1 (14%) | |
<50% | 94 (80%) | 1 (50%) | 9 (53%) | 5 (71%) | |
≥50% | 22 (19%) | 1 (50%) | 8 (47%) | 1 (14%) |
Variable | Estimate | Std. Error | z Value | p-Value | Odds Ratio | OR 95% CI |
---|---|---|---|---|---|---|
Loss of Both Heterodimers | 0.017 | 0.101 | 0.167 | 0.867 | 1.0171453 | 0.834–1.24 |
Loss of MLH1/PMS2 | 0.017 | 0.037 | 0.460 | 0.646 | 1.0171453 | 0.946–1.093 |
Loss of MSH2/MSH6 | −0.126 | 0.055 | −2.279 | 0.024 | 0.8816148 | 0.791–0.982 |
Variable | Estimate | Std. Error | t Value | p-Value | Odds Ratio | OR 95% CI |
---|---|---|---|---|---|---|
Loss of Both Heterodimers | 0.003 | 0.095 | 0.031 | 0.975 | 1.0030045 | 0.832–1.209 |
Loss of MLH1/PMS2 | −0.005 | 0.036 | −0.129 | 0.898 | 0.9950125 | 0.928–1.068 |
Loss of MSH2/MSH6 | −0.124 | 0.052 | −2.364 | 0.020 | 0.8833798 | 0.797–0.979 |
Grading 2 | 0.048 | 0.024 | 2.053 | 0.042 | 1.0491707 | 1.002–1.1 |
LVSI Focal | −0.184 | 0.044 | −4.173 | 0.001 | 0.8319358 | 0.763–0.907 |
LVSI Diffuse | −0.001 | 0.036 | −0.023 | 0.981 | 0.9990005 | 0.931–1.073 |
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Ronsini, C.; Restaino, S.; Di Donna, M.C.; Cucinella, G.; Solazzo, M.C.; De Franciscis, P.; Vizzielli, G.; Ludovisi, M.; Chiantera, V. Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study. J. Pers. Med. 2025, 15, 417. https://doi.org/10.3390/jpm15090417
Ronsini C, Restaino S, Di Donna MC, Cucinella G, Solazzo MC, De Franciscis P, Vizzielli G, Ludovisi M, Chiantera V. Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study. Journal of Personalized Medicine. 2025; 15(9):417. https://doi.org/10.3390/jpm15090417
Chicago/Turabian StyleRonsini, Carlo, Stefano Restaino, Mariano Catello Di Donna, Giuseppe Cucinella, Maria Cristina Solazzo, Pasquale De Franciscis, Giuseppe Vizzielli, Manuela Ludovisi, and Vito Chiantera. 2025. "Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study" Journal of Personalized Medicine 15, no. 9: 417. https://doi.org/10.3390/jpm15090417
APA StyleRonsini, C., Restaino, S., Di Donna, M. C., Cucinella, G., Solazzo, M. C., De Franciscis, P., Vizzielli, G., Ludovisi, M., & Chiantera, V. (2025). Microsatellite Instability and Myometrial Infiltration in Low-Grade Endometrial Cancer: A Focus on MMR Heterodimer Dysfunction by a Retrospective Multicentric Italian Study. Journal of Personalized Medicine, 15(9), 417. https://doi.org/10.3390/jpm15090417