Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations
Abstract
:1. Introduction
2. Materials and Methods
2.1. Data Source and Patient Cohort
2.2. Pathologic Review and Follow-Up
2.3. Immunohistochemistry
2.4. Next-Generation Sequencing
2.5. Statistical Analysis
3. Results
3.1. KMT2D Expression
3.2. KMT2D Alterations
4. Discussion
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Acknowledgments
Conflicts of Interest
References
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IHC | NGS | |||||||
---|---|---|---|---|---|---|---|---|
Overall | Stratified by KMT2D Staining | Overall | Stratified by KMT2D Variant | |||||
N = 51 | Negative, N = 19 | Positive, N = 32 | p-Value | N = 27 | Pathogenic, N = 5 | Non-Pathogenic, N = 22 | p-Value | |
Age | 73 (60, 79) | 73 (54, 78) | 73 (63, 78) | 0.7 | 71 (61, 80) | 61 (45, 71) | 73 (64, 80) | 0.2 |
Sex | 0.5 | 0.6 | ||||||
female | 24 (47%) | 10 (53%) | 14 (44%) | 12 (44%) | 3 (60%) | 9 (41%) | ||
male | 27 (53%) | 9 (47%) | 18 (56%) | 15 (56%) | 2 (40%) | 13 (59%) | ||
Pathological tumor stage | 0.8 | >0.9 | ||||||
pT1 | 14 (27%) | 6 (32%) | 8 (25%) | 8 (30%) | 2 (40%) | 6 (27%) | ||
pT2 | 6 (12%) | 1 (5.3%) | 5 (16%) | 1 (3.7%) | 0 (0%) | 1 (4.5%) | ||
pT3 | 20 (39%) | 8 (42%) | 12 (38%) | 11 (41%) | 2 (40%) | 9 (41%) | ||
pT4 | 7 (14%) | 2 (11%) | 5 (16%) | 5 (19%) | 1 (20%) | 4 (18%) | ||
pTa | 4 (7.8%) | 2 (11%) | 2 (6.2%) | 2 (7.4%) | 0 (0%) | 2 (9.1%) | ||
N stage | 0.3 | 0.5 | ||||||
pN0 | 8 (16%) | 2 (11%) | 6 (19%) | 4 (15%) | 0 (0%) | 4 (18%) | ||
pN1 | 6 (12%) | 2 (11%) | 4 (12%) | 5 (19%) | 2 (40%) | 3 (14%) | ||
pN2 | 4 (7.8%) | 0 (0%) | 4 (12%) | 3 (11%) | 0 (0%) | 3 (14%) | ||
pNx | 33 (65%) | 15 (79%) | 18 (56%) | 15 (56%) | 3 (60%) | 12 (55%) | ||
M stage | 0.8 | >0.9 | ||||||
M0 | 45 (88%) | 16 (84%) | 29 (91%) | 23 (85%) | 5 (100%) | 18 (82%) | ||
M1 | 3 (5.9%) | 2 (11%) | 1 (3.1%) | 2 (7.4%) | 0 (0%) | 2 (9.1%) | ||
Mx | 3 (5.9%) | 1 (5.3%) | 2 (6.2%) | 2 (7.4%) | 0 (0%) | 2 (9.1%) | ||
Grade | 0.7 | >0.9 | ||||||
HG | 39 (76%) | 14 (74%) | 25 (78%) | 19 (70%) | 4 (80%) | 15 (68%) | ||
LG | 12 (24%) | 5 (26%) | 7 (22%) | 8 (30%) | 1 (20%) | 7 (32%) | ||
Location | 0.8 | 0.02 | ||||||
multifocal | 9 (18%) | 3 (16%) | 6 (19%) | 6 (22%) | 3 (60%) | 3 (14%) | ||
pelvis | 34 (67%) | 13 (68%) | 21 (66%) | 19 (70%) | 1 (20%) | 18 (82%) | ||
proximal | 6 (12%) | 3 (16%) | 3 (9.4%) | 2 (7.4%) | 1 (20%) | 1 (4.5%) | ||
distal | 2 (3.9%) | 0 (0%) | 2 (6.2%) | |||||
Tumor side | 0.5 | 0.6 | ||||||
left | 24 (47%) | 10 (53%) | 14 (44%) | 14 (52%) | 2 (40%) | 12 (55%) | ||
right | 27 (53%) | 9 (47%) | 18 (56%) | 13 (48%) | 3 (60%) | 10 (45%) | ||
Number of positive lymph nodes | >0.9 | 0.3 | ||||||
0 | 8 (53%) | 2 (67%) | 6 (50%) | 4 (44%) | 0 (0%) | 4 (57%) | ||
1 | 4 (27%) | 1 (33%) | 3 (25%) | 3 (33%) | 2 (100%) | 1 (14%) | ||
3 | 2 (13%) | 0 (0%) | 2 (17%) | 1 (11%) | 0 (0%) | 1 (14%) | ||
5 | 1 (6.7%) | 0 (0%) | 1 (8.3%) | 1 (11%) | 0 (0%) | 1 (14%) | ||
Chemotherapy | 13 (26%) | 3 (17%) | 10 (31%) | 0.3 | 9 (35%) | 1 (25%) | 8 (36%) | >0.9 |
Metastasis | 19 (37%) | 6 (32%) | 13 (41%) | 0.5 | 13 (48%) | 2 (40%) | 11 (50%) | >0.9 |
History of bladder cancer | 8 (16%) | 0 (0%) | 8 (25%) | 0.02 | 2 (7.4%) | 0 (0%) | 2 (9.1%) | >0.9 |
Recurrence | 22 (43%) | 7 (37%) | 15 (47%) | 0.5 | 11 (41%) | 1 (20%) | 10 (45%) | 0.6 |
Site of recurrence | >0.9 | 0.6 | ||||||
bladder | 19 (37%) | 7 (37%) | 12 (38%) | 9 (33%) | 1 (20%) | 8 (36%) | ||
no | 32 (63%) | 12 (63%) | 20 (62%) | 18 (67%) | 4 (80%) | 14 (64%) | ||
Patient died | 23 (45%) | 7 (37%) | 16 (50%) | 0.4 | 14 (52%) | 3 (60%) | 11 (50%) | >0.9 |
Months to Death/Censor | 29 (8, 80) | 10 (4, 26) | 36 (16, 102) | 0.036 | 18 (6, 60) | 7 (1, 30) | 20 (8, 64) | 0.2 |
Median (IQR); n (%) |
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Laukhtina, E.; Lemberger, U.; Bruchbacher, A.; Ilijazi, D.; Korn, S.; Berndl, F.; D’Andrea, D.; Susani, M.; Enikeev, D.; Compérat, E.; et al. Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations. J. Pers. Med. 2021, 11, 1147. https://doi.org/10.3390/jpm11111147
Laukhtina E, Lemberger U, Bruchbacher A, Ilijazi D, Korn S, Berndl F, D’Andrea D, Susani M, Enikeev D, Compérat E, et al. Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations. Journal of Personalized Medicine. 2021; 11(11):1147. https://doi.org/10.3390/jpm11111147
Chicago/Turabian StyleLaukhtina, Ekaterina, Ursula Lemberger, Andreas Bruchbacher, Dafina Ilijazi, Stephan Korn, Florian Berndl, David D’Andrea, Martin Susani, Dmitry Enikeev, Eva Compérat, and et al. 2021. "Expression Analysis and Mutational Status of Histone Methyltransferase KMT2D at Different Upper Tract Urothelial Carcinoma Locations" Journal of Personalized Medicine 11, no. 11: 1147. https://doi.org/10.3390/jpm11111147