TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients
Abstract
:Simple Summary
Abstract
1. Introduction
2. Results
2.1. Baseline Characteristics
2.2. Associations between TERT Promoter Mutation Status and Clinicopathological Variables
2.3. Associations between TERT Promoter Mutation Status or Clinicopathological Variables and Thyroid Cancer-Specific Survival
3. Discussion
4. Materials and Methods
4.1. Patients and Clinicopathological Data
4.2. DNA Isolation from Thyroid Cancer Samples
4.3. Detection of TERT Promoter and BRAF T1799A Mutations
4.4. Statistical Analysis
5. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | DTC (n = 393), N (%) | PTC (n = 327), N (%) |
---|---|---|
Sex | - | - |
Female | 329 (83.7) | 276 (84.4) |
Male | 64 (16.3) | 51 (15.6) |
Age, years | - | - |
Median | 43 | 43 |
Range | 16–81 | 16–81 |
<55 | 319 (81.2) | 265 (81.0) |
≥55 | 74 (18.8) | 62 (19.0) |
TERT promoter status | - | - |
Wild-type | 350 (89.1) | 295 (90.2) |
Mutation | 43 (10.9) | 32 (9.8) |
BRAF mutation | - | - |
Wild-type | 117 (37.0) | 65 (24.6) |
Mutation | 199 (63.0) | 199 (75.4) |
Missing data | 77 | 63 |
Histologic type | - | - |
PTC | 327 (83.2) | - |
FTC | 66 (16.8) | - |
Multifocality | - | - |
Absent | 286 (72.8) | 228 (69.7) |
Present | 107 (27.2) | 99 (30.3) |
Lymph node metastasis | - | - |
Absent | 199 (50.6) | 135 (41.3) |
Present | 193 (49.1) | 191 (58.4) |
Missing data | 1 (0.3) | 1 (0.3) |
Extrathyroidal extension | - | - |
Absent | 352 (89.6) | 290 (88.7) |
Present | 41 (10.4) | 37 (11.3) |
Distant metastasis | - | - |
Absent | 370 (94.1) | 313 (95.7) |
Present | 23 (5.9) | 14 (4.3) |
Stage at diagnosis a | - | - |
I | 329 (83.7) | 274 (83.8) |
II | 48 (12.2) | 42 (12.8) |
III and IV | 16 (4.1) | 11 (3.4) |
Tumor size, cm | - | - |
Median | 2.7 | 2.5 |
Range | 0.4–12.0 | 0.4–10.5 |
<2.0 | 45 (11.5) | 35 (10.7) |
2.0–4.0 | 293 (74.6) | 253 (77.4) |
>4.0 | 55 (14.0) | 39 (11.9) |
RAI total dose, mCi | - | - |
Median | 130 | 160 |
Range | 0–1400 | 0–1250 |
Variables | DTC | |||
---|---|---|---|---|
TERT WT, N (%) | TERT Mut, N (%) | OR a (95%CI) | p-Value | |
Sex | - | - | - | - |
Female | 293 (89.1) | 36 (10.9) | 1.00 (reference) | 0.999 |
Male | 57 (89.1) | 7 (10.9) | 1.00 (0.39–2.23) | - |
Age, years | - | - | - | - |
Per 5 years | - | - | 1.94 (1.64–2.35) | <0.001 |
<55 | 304 (95.3) | 15 (4.7) | 1.00 (reference) | <0.001 |
≥55 | 46 (62.2) | 28 (37.8) | 12.34 (6.22–25.39) | - |
BRAF mutation | - | - | - | - |
Wild-type | 107 (91.5) | 10 (8.5) | 1.00 (reference) | 0.333 |
Mutant | 175 (87.9) | 24 (12.1) | 1.47 (0.69–3.33) | - |
Missing data | 68 (88.3) | 9 (11.7) | - | - |
Histologic type | - | - | - | - |
PTC | 295 (90.2) | 32 (9.8) | 1.00 (reference) | 0.107 |
FTC | 55 (83.3) | 11 (16.7) | 1.84 (0.84–3.78) | - |
Multifocality | - | - | - | - |
Absent | 255 (89.2) | 31 (10.8) | 1.00 (reference) | 0.915 |
Present | 95 (88.8) | 12 (11.2) | 1.04 (0.49–2.06) | - |
Lymph node metastasis | - | - | - | - |
Absent | 179 (89.9) | 20 (10.1) | 1.00 (reference) | 0.666 |
Present | 171 (88.6) | 22 (11.4) | 1.15 (0.61–2.20) | - |
Missing data | 0 (0.0) | 1 (100) | - | - |
Extrathyroidal extension | - | - | - | - |
Absent | 322 (91.5) | 30 (8.5) | 1.00 (reference) | <0.001 |
Present | 28 (68.3) | 13 (31.7) | 4.98 (2.29–10.51) | - |
Distant metastasis | - | - | - | - |
Absent | 335 (90.5) | 35 (9.5) | 1.00 (reference) | 0.001 |
Present | 15 (65.2) | 8 (34.8) | 5.10 (1.94–12.64) | - |
Stage at diagnosis b | - | - | - | - |
I | 313 (95.1) | 16 (4.9) | 1.00 (reference) | <0.001 |
II | 31 (64.6) | 17 (35.4) | 10.73 (4.94–23.56) | <0.001 |
III and IV | 6 (37.5) | 10 (62.5) | 32.60 (10.81–107.06) | <0.001 |
Tumor size, cm | - | - | - | - |
<2.0 | 41 (91.1) | 4 (8.9) | 1.00 (reference) | 0.375 |
2.0–4.0 | 263 (89.8) | 30 (10.2) | 1.17 (0.43–4.09) | 0.779 |
>4.0 | 46 (83.6) | 9 (16.4) | 2.01 (0.60–7.85) | 0.275 |
RAI total dose, mCi | - | - | - | - |
Median (range) | 130 (0–1200) | 230 (0–1400) | 1.002 (1.001–1.003) | <0.001 |
Variables | N a | 10-Year Survival Rate (%) | Univariate Cox Models | Multivariate Cox Model 1 b (Extended Model) | Multivariate Cox Model 2 c (Restricted Model) | |||
---|---|---|---|---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |||
Sex | - | - | - | - | - | - | - | - |
Female | 329 | 95.1 | 1.00 (reference) | - | 1.00 (reference) | 0.099 | 1.00 (reference) | 0.054 |
Male | 64 | 92.2 | 1.83 (0.78–4.34) | 0.167 | 2.27 (0.86–5.98) | - | 2.46 (0.99–6.15) | - |
Age, years d | - | - | - | - | - | - | - | - |
Per 5 years | 393 | - | 1.75 (1.50–2.06) | <0.001 | 1.46 (1.18–1.79) | <0.001 | - | - |
<55 | 319 | 97.5 | 1.00 (reference) | <0.001 | - | - | - | - |
≥55 | 74 | 82.4 | 11.34 (4.96–25.93) | - | - | - | - | - |
TERT mutation | - | - | - | - | - | - | - | - |
Wild-type | 350 | 98.0 | 1.00 (reference) | <0.001 | 1.00 (reference) | 0.002 | 1.00 (reference) | <0.001 |
Mutant | 43 | 67.4 | 24.15 (10.56–55.25) | - | 5.18 (1.81–14.82) | - | 9.93 (3.67–26.90) | - |
BRAF mutation | - | - | - | - | - | - | - | - |
Wild-type | 117 | 92.3 | 1.00 (reference) | 0.331 | - | - | - | - |
Mutant | 199 | 97.0 | 0.64 (0.26–1.57) | - | - | - | - | - |
Histologic type | - | - | - | - | - | - | - | - |
PTC | 327 | 96.6 | 1.00 (reference) | 0.004 | 1.00 (reference) | 0.028 | 1.00 (reference) | 0.001 |
FTC | 66 | 84.8 | 3.15 (1.44–6.88) | - | 3.02 (1.13–8.09) | - | 4.11 (1.77–9.54) | - |
Multifocality | - | - | - | - | - | - | - | - |
Absent | 286 | 94.4 | 1.00 (reference) | 0.847 | - | - | - | - |
Present | 107 | 95.3 | 0.92 (0.39–2.17) | - | - | - | - | - |
Lymph node metastasis | - | - | - | - | - | - | - | - |
Absent | 199 | 94.0 | 1.00 (reference) | 0.964 | - | - | - | - |
Present | 193 | 95.3 | 1.02 (0.47–2.20) | - | - | - | - | - |
Extrathyroidal extension | - | - | - | - | - | - | - | - |
Absent | 352 | 96.0 | 1.00 (reference) | <0.001 | 1.00 (reference) | 0.227 | - | - |
Present | 41 | 82.9 | 4.78 (2.14–10.64) | - | 1.81 (0.69–4.75) | - | - | - |
Distant metastasis | - | - | - | - | - | - | - | - |
Absent | 370 | 96.8 | 1.00 (reference) | <0.001 | 1.00 (reference) | 0.063 | - | - |
Present | 23 | 60.9 | 10.85 (4.86–24.22) | - | 2.61 (0.95–7.20) | - | - | - |
Stage at diagnosis e | - | - | - | - | - | - | - | - |
I | 329 | 97.6 | 1.00 (reference) | <0.001 | - | - | 1.00 (reference) | 0.003 |
II | 48 | 85.4 | 10.42 (4.19–25.92) | <0.001 | - | - | 5.00 (1.73–14.50) | 0.003 |
III and IV | 16 | 62.5 | 26.82 (10.03–71.70) | <0.001 | - | - | 6.57 (2.04–21.12) | 0.002 |
Tumor size, cm | - | - | - | - | - | - | - | - |
<2.0 | 45 | 95.6 | 1.00 (reference) | 0.014 | 1.00 (reference) | 0.298 | - | - |
2.0–4.0 | 293 | 95.9 | 1.24 (0.28–5.38) | 0.776 | 0.77 (0.16–3.65) | 0.744 | - | - |
>4.0 | 55 | 87.3 | 3.96 (0.86–18.34) | 0.078 | 1.61 (0.30–8.67) | 0.582 | - | - |
Variables | N a | 10-Year Survival Rate (%) | Univariate Cox Models | Multivariate Cox Model 1 b (Extended Model) | Multivariate Cox Model 2 c (Restricted Model) | |||
---|---|---|---|---|---|---|---|---|
HR (95% CI) | p-Value | HR (95% CI) | p-Value | HR (95% CI) | p-Value | |||
Sex | - | - | - | - | - | - | - | - |
Female | 276 | 97.5 | 1.00 (reference) | 0.026 | 1.00 (reference) | 0.244 | 1.00 (reference) | 0.072 |
Male | 51 | 92.2 | 3.09 (1.14–8.36) | - | 2.07 (0.61–7.02) | - | 2.57 (0.92–7.22) | - |
Age, years d | - | - | - | - | - | - | - | - |
Per 5 years | 327 | - | 1.73 (1.42–2.10) | <0.001 | 1.30 (0.99–1.70) | 0.059 | - | - |
<55 | 265 | 98.1 | 1.00 (reference) | <0.001 | - | - | - | - |
≥55 | 62 | 90.3 | 11.00 (3.87–31.23) | - | - | - | - | - |
TERT mutation | - | - | - | - | - | - | - | - |
Wild-type | 295 | 99.0 | 1.00 (reference) | <0.001 | 1.00 (reference) | 0.002 | 1.00 (reference) | <0.001 |
Mutant | 32 | 75.0 | 36.27 (11.81–111.42) | - | 10.68 (2.36–48.27) | - | 18.55 (4.83–71.18) | - |
BRAF mutation | - | - | - | - | - | - | - | - |
Wild-type | 65 | 98.5 | 1.00 (reference) | 0.253 | - | - | - | - |
Mutant | 199 | 97.0 | 3.31 (0.42–25.89) | - | - | - | - | - |
Multifocality | - | - | - | - | - | - | - | - |
Absent | 228 | 96.9 | 1.00 (reference) | 0.664 | - | - | - | - |
Present | 99 | 96.0 | 1.25 (0.46–3.37) | - | - | - | - | - |
Lymph node metastasis | - | - | - | - | - | - | - | - |
Absent | 135 | 97.0 | 1.00 (reference) | 0.410 | - | - | - | - |
Present | 191 | 96.3 | 1.56 (0.54–4.49) | - | - | - | - | - |
Extrathyroidal extension | - | - | - | - | - | - | - | - |
Absent | 290 | 97.6 | 1.00 (reference) | 0.002 | 1.00 (reference) | 0.230 | - | - |
Present | 37 | 89.2 | 4.67 (1.73–12.65) | - | 2.06 (0.63–6.70) | - | - | - |
Distant metastasis | - | - | - | - | - | - | - | - |
Absent | 313 | 97.4 | 1.00 (reference) | 0.007 | 1.00 (reference) | 0.199 | - | - |
Present | 14 | 78.6 | 5.59 (1.61–19.47) | - | 2.85 (0.58–14.12) | - | - | - |
Stage at diagnosis e | - | - | - | - | - | - | - | - |
I | 274 | 98.2 | 1.00 (reference) | <0.001 | - | - | 1.00 (reference) | 0.221 |
II | 42 | 92.9 | 9.60 (3.05–30.25) | <0.001 | - | - | 2.65 (0.72–9.78) | 0.142 |
III and IV | 11 | 72.7 | 31.06 (8.97–107.58) | <0.001 | - | - | 3.45 (0.79–15.07) | 0.099 |
Tumor size, cm | - | - | - | - | - | - | - | - |
<2.0 | 35 | 97.1 | 1.00 (reference) | 0.087 | 1.00 (reference) | 0.486 | - | - |
2.0–4.0 | 253 | 97.2 | 1.53 (0.20–11.84) | 0.685 | 0.75 (0.09–6.19) | 0.790 | - | - |
>4.0 | 39 | 92.3 | 4.70 (0.55–40.19) | 0.158 | 1.57 (0.15–16.21) | 0.706 | - | - |
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Park, J.; Lee, S.; Kim, K.; Park, H.; Ki, C.-S.; Oh, Y.L.; Shin, J.H.; Kim, J.S.; Kim, S.W.; Chung, J.H.; et al. TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients. Cancers 2021, 13, 648. https://doi.org/10.3390/cancers13040648
Park J, Lee S, Kim K, Park H, Ki C-S, Oh YL, Shin JH, Kim JS, Kim SW, Chung JH, et al. TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients. Cancers. 2021; 13(4):648. https://doi.org/10.3390/cancers13040648
Chicago/Turabian StylePark, Jun, Sungjoo Lee, Kyunga Kim, Hyunju Park, Chang-Seok Ki, Young Lyun Oh, Jung Hee Shin, Jee Soo Kim, Sun Wook Kim, Jae Hoon Chung, and et al. 2021. "TERT Promoter Mutations and the 8th Edition TNM Classification in Predicting the Survival of Thyroid Cancer Patients" Cancers 13, no. 4: 648. https://doi.org/10.3390/cancers13040648