Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Study Population and Data Collection
2.2. Molecular Classification
2.3. Statistical Analyses
3. Results
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Age (Years) (Median (Interquartile Range)) | 68 (60–75) |
---|---|
Body mass index (kg/m2) (edian (interquartile range)) | 27.3 (23.7–32.4) |
Pelvic lymphadenectomy | 447 (56.2%) |
Pelvic-aortic lymphadenectomy | 118 (14.8%) |
Stage | |
IA | 431 (54.2%) |
IB | 164 (20.6%) |
II | 54 (6.8%) |
IIIA | 39 (4.9%) |
IIIB | 7 (0.9%) |
IIIC1 | 46 (5.8%) |
IIIC2 | 24 (3.0%) |
IVA | 0 (0%) |
IVB | 30 (3.8%) |
Mismatch repair deficiency | 287 (36.1%) |
Histology | |
Endometrioid carcinoma | 702 (88.3%) |
Clear cell carcinoma | 32 (4.0%) |
Serous carcinoma | 29 (3.6%) |
Carcinosarcoma | 17 (2.1%) |
Undifferentiated carcinoma | 14 (1.8%) |
Neuroendocrine carcinoma | 1 (0.1%) |
Grade (For endometrioid only, n = 702) | |
1 | 402 (57.3%) |
2 | 193 (27.5%) |
3 | 107 (15.2%) |
Aberrant p53 1 | 134 (17.1%) |
Polymerase-ϵ ultramutated 2 | 33 (6.4%) |
Adjuvant therapy | |
Vaginal brachytherapy | 383 (48.2%) |
Whole pelvic radiotherapy | 115 (14.5%) |
Chemotherapy | 34 (4.3%) |
Chemotherapy and vaginal brachytherapy | 50 (6.3%) |
Chemotherapy and whole pelvic radiotherapy | 100 (12.6%) |
Variable | MMR-D (n = 191) | NSMP (n = 218) | p |
---|---|---|---|
Age (years) (median (interquartile range)) | 70 (61–77) | 66 (60–73) | 0.003 |
Body mass index (kg/m2) (median (interquartile range)) | 27.1 (23.3–32.7) | 28.5 (24.3–33.2) | 0.042 |
Pelvic lymphadenectomy | 106 (55.5%) | 129 (59.2%) | 0.453 |
Pelvic-aortic lymphadenectomy | 34 (17.8%) | 19 (8.7%) | 0.006 |
Stage | 0.077 | ||
IA | 84 (44.0%) | 123 (56.4%) | |
IB | 44 (23.0%) | 42 (19.3%) | |
II | 19 (9.9%) | 23 (10.6%) | |
IIIA | 13 (6.8%) | 9 (4.1%) | |
IIIB | 2 (1.0%) | 1 (0.5%) | |
IIIC1 | 18 (9.4%) | 13 (6.0%) | |
IIIC2 | 7 (3.7%) | 1 (0.5%) | |
IVA | 0 (0%) | 0 (0%) | |
IVB | 4 (2.1%) | 6 (2.8%) | |
Histology | <0.001 | ||
Endometrioid grade 1–2 | 133 (69.6%) | 193 (88.5%) | |
Endometrioid grade 3 | 41 (21.5%) | 13 (6.0%) | |
Nonendometrioid | 17 (8.9%) 1 | 12 (5.5%) 2 | |
Myometrial invasion ≥ 50% | 89 (46.6%) | 83 (38.1%) | 0.081 |
Cervical stromal invasion | 42 (22.1%) 3 | 31 (14.2%) | 0.038 |
Tumor size > 5 cm | 49 (27.4%) 4 | 44 (21.8%) 5 | 0.205 |
Lymphovascular space invasion | 62 (32.5%) | 49 (22.5%) | 0.023 |
Positive peritoneal cytology | 10 (5.3%) 6 | 11 (5.1%) 7 | 0.917 |
L1 cell adhesion molecule | 17 (8.9%) 3 | 14 (6.7%) 8 | |
Adjuvant therapy | 0.081 | ||
Vaginal brachytherapy | 83 (43.5%) | 116 (53.2%) | |
Whole pelvic radiotherapy | 35 (18.3%) | 28 (12.8%) | |
Chemotherapy | 8 (4.2%) | 7 (3.2%) | |
Chemotherapy and vaginal brachytherapy | 10 (5.2%) | 10 (4.6%) | |
Chemotherapy and whole pelvic radiotherapy | 35 (18.3%) | 24 (11.0%) |
Variable | n | HR (95% CI) | p |
---|---|---|---|
Mismatch repair deficiency | 173 | 2.0 (1.1–3.6) | 0.024 |
Age (continuous variable) | 364 | 1.0 (0.98–1.0) | 0.635 |
Stage II–IV | 104 | 2.0 (0.71–5.6) | 0.188 |
Histology | 0.111 | ||
Endometrioid grade 1–2 | 289 | 1 | |
Endometrioid grade 3 | 48 | 2.0 (1.0–3.9) | 0.041 |
Nonendometrioid | 27 | 1.6 (0.72–3.7) | 0.239 |
Myometrial invasion ≥ 50% | 148 | 2.2 (1.1–4.4) | 0.033 |
Cervical stromal invasion | 67 | 0.59 (0.28–1.2) | 0.162 |
Tumor size > 5 cm | 91 | 1.8 (1.0–3.3) | 0.047 |
Lymphovascular space invasion | 99 | 2.6 (1.4–4.7) | 0.001 |
Positive peritoneal cytology | 19 | 4.3 (2.1–9.0) | <0.001 |
Positive L1 cell adhesion molecule | 28 | 1.5 (0.69–3.3) | 0.306 |
Adjuvant therapy | 0.882 | ||
None | 48 | 1 | |
Vaginal brachytherapy | 175 | 0.60 (0.17–2.1) | 0.421 |
Whole pelvic radiotherapy | 57 | 0.72 (0.22–2.4) | 0.591 |
Chemotherapy ± VBT/WPRT | 84 | 0.81 (0.25–2.6) | 0.719 |
Variable | N MMR-D (n = 191) | N NSMP (n = 218) | HR (95% CI) (ref: NSMP) | p |
---|---|---|---|---|
Age ≤ 65 years | 70 (36.6%) | 102 (46.8%) | 2.9 (1.2–6.8) | 0.015 |
Age > 65 years | 121 (63.4%) | 116 (53.2%) | 1.8 (1.0–3.3) | 0.051 |
Low-risk histology 1 | 133 (69.6%) | 193 (88.5%) | 2.8 (1.4–5.6) | 0.003 |
High-risk histology 2 | 58 (30.4%) | 25 (11.5%) | 0.70 (0.35–1.4) | 0.332 |
Myometrial invasion < 50% | 102 (53.4%) | 135 (61.9%) | 2.8 (1.0–7.4) | 0.041 |
Myometrial invasion ≥ 50 | 89 (46.6%) | 83 (38.1%) | 1.8 (0.99–3.1) | 0.053 |
Cervical stromal invasion − | 148 (77.9%) 3 | 187 (85.8%) | 2.0 (1.1–3.5) | 0.024 |
Cervical stromal invasion + | 42 (22.1%) | 31 (14.2%) | 2.3 (0.92–6.0) | 0.073 |
Tumor size ≤ 5 cm | 130 (72.6%) 4 | 158 (78.2%) 5 | 2.3 (1.1–4.5) | 0.020 |
Tumor size > 5 cm | 49 (27.4%) | 44 (21.8%) | 1.7 (0.80–3.5) | 0.170 |
Lymphovascular space invasion − | 129 (67.5%) | 169 (77.5%) | 2.2 (1.0–4.9) | 0.046 |
Lymphovascular space invasion + | 62 (32.5%) | 49 (22.5%) | 1.7 (0.89–3.1) | 0.108 |
Peritoneal cytology − | 177 (94.7%) 6 | 204 (94.9%) 7 | 3.1 (1.7–5.7) | <0.001 |
Peritoneal cytology + | 10 (5.3%) | 11 (5.1%) | 0.73 (0.25–2.1) | 0.567 |
L1 cell adhesion molecule − | 173 (91.1%) 3 | 196 (93.3%) 8 | 2.9 (1.6–5.1) | <0.001 |
L1 cell adhesion molecule + | 17 (8.9%) | 14 (6.7%) | 0.76 (0.25–2.4) | 0.639 |
Relapse Type | MMR-D (n = 128) | NSMP (n = 165) | p |
---|---|---|---|
Vaginal | 0 (0%) | 4 (2.4%) | 0.134 |
Pelvic | 11 (8.6%) | 4 (2.4%) | 0.029 |
Other intra-abdominal | 3 (2.3%) | 7 (4.2%) | 0.522 |
Extra-abdominal | 5 (3.9%) | 3 (1.8%) | 0.303 |
Type of Lymph Node Metastasis or Relapse | MMR-D (n = 191) | NSMP (n = 218) | p |
---|---|---|---|
Stage IIIC1 | 18 (9.4%) | 13 (6.0%) | |
Stage IIIC2 | 7 (3.7%) | 1 (0.5%) | |
Stage IV with lymph node involvement | 1 (0.5%) | 1 (0.5%) | |
Stage IV with lymph node relapse | 3 (1.6%) | 1 (0.5%) | |
Stage I–IIIB with pelvic lymph node relapse | 5 (2.6%) | 3 (1.4%) | |
Stage I–IIIB with para-aortic lymph node relapse | 2 (1.0%) | 3 (1.4%) | |
Stage I–IIIB with pelvic-aortic lymph node relapse | 2 (1.0%) | 1 (0.5%) | |
Combined | 38 (19.9%) | 23 (10.6%) | 0.008 |
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Loukovaara, M.; Pasanen, A.; Bützow, R. Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma. Cancers 2021, 13, 3124. https://doi.org/10.3390/cancers13133124
Loukovaara M, Pasanen A, Bützow R. Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma. Cancers. 2021; 13(13):3124. https://doi.org/10.3390/cancers13133124
Chicago/Turabian StyleLoukovaara, Mikko, Annukka Pasanen, and Ralf Bützow. 2021. "Mismatch Repair Deficiency as a Predictive and Prognostic Biomarker in Molecularly Classified Endometrial Carcinoma" Cancers 13, no. 13: 3124. https://doi.org/10.3390/cancers13133124