FIGURE 1.
Flowchart of the present study.
EC = endometrial carcinoma
TABLE 1.
Imaging protocol parameters
| Parameters | T1WI | T2WI | DWI | IVIM | DCE-MRI |
|---|---|---|---|---|---|
| Sequence | 2D-FSE | 2D-FSE | 2D-SS-EPI | 2D-SS-EPI | 3D-LAVA |
| Orientation | Oblique Axial | Oblique Axial | Oblique Axial | Oblique Axial | Oblique Axial |
| TR/TE (ms) | 659/12.3 | 6000/95 | 3708/74.3 | 2000/80.7 | 3.5/1.7 |
| FOV (cm2) | 40 × 40 | 40 × 40 | 40 × 40 | 40 × 40 | 36 × 36 |
| Matrix | 288 × 192 | 320 × 320 | 96 × 128 | 128 × 192 | 288 × 192 |
| Flip angle (°) | 160 | 160 | 90 | 90 | 15 |
| Slice thickness (mm) | 6 | 6 | 6 | 6 | 6 |
| No. of sections | 20 | 20 | 20 | Based on lesion's size | 26 |
| NEX | 1 | 1 | 1, 4 | 1, 1, 1, 1, 1, 1, 2, 4, 4, 6 | 0.73 |
| Fat suppression | / | STIR | STIR | STIR | FLEX |
| b-values (s/mm2) | / | / | 0, 800 | 0, 20, 40, 80, 160, 200, 400, 600, 800, 1000 | / |
| Respiratory compensation | Free | Free | Free | Free | Free |
| Scan time | 1 min 56 s | 48 s | 1 min 04 s | 3~6min | 6 min 08 s (40 phases) |
[i] DCE-MRI = dynamic contrast-enhanced magnetic resonance imaging; DWI = diffusion-weighted imaging; FOV = field of view; FLEX = FLEXible; FSE = fast spin echo; IVIM = intravoxel incoherent motion; LAVA = liver acquistion with volume assessmeNT; NEX = number of excitations; SS-EPI = single shot echo planar imaging; STIR = short-inversion time(TI) recovery; TR/TE = repetition time/echo time; T1WI = T1-weighted imaging; T2WI = T2-weighted imaging
TABLE 2.
Clinicopathologic features of the patients
| Variable | Data |
|---|---|
| Age (mean ± SD) (years) | 54.00 ± 7.91 |
| Maximum diameter (mean ± SD) (mm) | 25.10 (13.76, 42.58) |
| FIGO stage n (%) | |
| IA | 44 (59.46) |
| IB | 30 (40.54) |
| Histologic subtype n (%) | |
| Adenocarcinoma | 67 (90.54) |
| Non-adenocarcinoma | 7 (9.46) |
| Clear-cell | 3 (4.06) |
| Undifferentiated carcinoma | 2 (2.70) |
| Carcinosarcoma | 2 (2.70) |
| Lymphovascular space invasion n (%) | |
| Positive | 10 (6.76) |
| Negative | 64 (93.24) |
| Histologic grade n (%) | |
| Grade 1 | 54 (72.98) |
| Grade 2 | 10 (13.51) |
| Grade 3 | 10 (13.51) |
| Risk stratification n (%) | |
| Low | 44 (59.46) |
| Intermediate | 20 (27.03) |
| High-intermediate | 0 (0.00) |
| High | 10 (13.51) |
| TP53 expression | |
| Mutant | 21 (28.38) |
| Wild | 25 (33.78) |
| No result | 28 (37.84) |
[i] FIGO = International Federation of Gynecology and Obstetrics; SD = standard deviation
FIGURE 2.
(A–I) A 53-year-old woman with low-risk endometrial carcinoma (EC) (arrowheads, endometrioid type, grade 2, stage IA, lymphovascular space invasion (LVSI) negative, and TP53-wild). (J–R) A 56-year-old woman with non-low-risk (intermediate) EC (arrowheads, endometrioid type, grade 1, stage IB, LVSI negative, and TP53-mutant). (A, J) Sagittal T2-weighted imaging maps; (B, K) Oblique axial pseudo colored maps of volume transfer constant (Ktrans); (C, L) Oblique axial pseudo colored maps of rate transfer constant (Kep); (D, M) Oblique axial pseudo colored maps of the volume of extravascular extracellular space per unit volume of tissue (Ve); (E, N) Oblique axial colored maps of true diffusion coefficient (D); (F, O) Oblique axial colored maps of pseudo-diffusion coefficient (D*); (G, P) Oblique axial colored maps of microvascular volume fraction (f), and (H, Q) Histopathological images (magnification = 100), and (I, R) Immunohistochemical image (magnification = 200).
TABLE 3.
Comparison of different parameters
| Parameters | D (×10−3mm2/s) | D* (×10−3mm2/s) | f (%) | Ktrans (min−1) | Ve | Kep(min−1) |
|---|---|---|---|---|---|---|
| Risk stratification | ||||||
| High-risk (n = 10) | 0.63 (0.40, 0.73) | 58.40 (40.10, 88.73) | 1.64 ± 0.60 | 0.35 (0.15, 0.43) | 0.30 ± 0.07 | 1.23 (0.48, 1.54) |
| High-intermediate-risk (n = 0) | / | / | / | / | / | / |
| Intermediate-risk (n = 20) | 0.55 (0.40, 0.81) | 52.00 (26.88, 74.33) | 1.74 ± 0.96 | 0.37 (0.29, 0.47) | 0.33 ± 0.14 | 1.24 (0.82, 1.98) |
| Low-risk (n = 44) | 0.86 (0.64, 1.16) | 44.35 (21.93, 95.33) | 2.43 ± 1.08 | 0.61 (0.43, 1.14) | 0.58 ± 0.25 | 1.53 (0.79, 2.21) |
| P-value | 0.033 a | 0.464 a | 0.012 a | < 0.001 a | < 0.001 a | 0.191 a |
| P-value (High vs Intermediate) | 0.880 b | 0.248 b | 0.735 c | 0.397 b | 0.532 c | 0.307 b |
| P-value (High vs Low) | 0.009 b | 0.238 b | 0.004 c | < 0.001 b | 0.001 c | 0.099 b |
| P-value (Intermediate vs Low) | 0.001 b | 0.937 b | 0.014 c | < 0.001 b | < 0.001 c | 0.582 |
| Low-risk (n = 44) | 0.86 (0.64, 1.16) | 44.35 (21.93, 95.33) | 2.43 ± 1.08 | 0.61 (0.43, 1.14) | 0.58 ± 0.25 | 1.53 (0.79, 2.21) |
| Non-low-risk (High + Intermediate, n = 30) | 0.58 (0.40, 0.77) | 55.25 (34.63, 72.78) | 1.71 ± 0.84 | 0.37 (0.28, 0.45) | 0.32 ± 0.12 | 1.23 (0.82, 1.87) |
| z/t value | − 3.793 | −0.523 | 3.234 | −5.109 | 5.304 | −1.233 |
| P-value | < 0.001 b | 0.601 b | 0.002 c | < 0.001 b | < 0.001 c | 0.218 b |
| TP53 expression | ||||||
| Mutant (n = 21) | 0.72 ± 0.31 | 43.70 (16.30, 90.75) | 2.30 ± 1.09 | 0.67 (0.41, 1.14) | 0.32 (0.25, 0.91) | 1.67 (1.17, 2.09) |
| Wild (n = 25) | 0.91 ± 0.29 | 50.60 (26.90, 82.75) | 2.20 ± 1.02 | 0.43 (0.37, 0.49) | 0.49 (0.36, 0.76) | 0.90 (0.58, 1.55) |
| Z/t value | −2.155 | −0.518 | 0.321 | −2.073 | −0.783 | −3.165 |
| P-value | 0.037 c | 0.604 b | 0.750 c | 0.038 b | 0.434 b | 0.002 b |
FIGURE 3.
Plots show individual data points, averages, and standard deviations of true diffusion coefficient (D) (A, G), pseudo-diffusion coefficient (D*) (B, H), microvascular volume fraction (f) (C, I), volume transfer constant (Ktrans) (D, J), the volume of extravascular extracellular space per unit volume of tissue (Ve) (E, K), and rate transfer constant (Kep) (F, L) in low-risk and non-low-risk groups (A–F), TP53-mutant and TP53-wild groups (G–L). Individual points are averages of values calculated by 2 readers. *P < 0.05, **P < 0.01, ***P < 0.001, and ● P > 0.005.
TABLE 4.
Logistic regression analyses
| Parameters | Univariate Analyses | P-value | Multivariate Analyses | P-value |
|---|---|---|---|---|
| OR for 1 SD (95% CI) | OR for 1 SD (95% CI) | |||
| Low vs non-low risk | ||||
| Age (year) | 1.462 (0.894–2.388) | 0.130 | / | / |
| Tumor size (mm) | 1.055 (1.003–1.110) | 0.038 | 1.083 (0.979–1.197) | 0.123 |
| TP53 mutant | 1.506 (0.407–5.578) | 0.540 | / | / |
| D (×10−3mm2/s) | 0.089 (0.021–0.373) | 0.001 | 0.144 (0.015–1.334) | 0.088 |
| D* (×10−3mm2/s) | 0.867 (0.533–1.412) | 0.567 | / | / |
| f (%) | 0.419 (0.226–0.776) | 0.006 | 0.292 (0.093–0.921) | 0.036 |
| Ktrans (min−1) | 0.009 (0.001–0.153) | 0.001 | 0.001 (0.000–0.089) | 0.003 |
| Ve | 0.173 (0.069–0.432) | < 0.001 | 0.130 (0.022–0.766) | 0.024 |
| Kep (min−1) | 0.642 (0.367–1.126) | 0.122 | / | / |
| TP53 mutant vs wild | ||||
| Age (year) | 0.855 (0.465–1.548) | 0.605 | / | / |
| Tumor size (mm) | 1.175 (0.649–2.127) | 0.594 | / | / |
| Subtype | 77.708 (0.001–100.5) | 0.999 | / | / |
| Grade | 2.099 (0.957–4.602) | 0.064 | 1.961 (0.816–4.717) | 0.132 |
| Risk stratification | 1.506 (0.407–5.578) | 0.540 | / | / |
| FIGO stage | 1.360 (0.739–2.505) | 0.323 | / | / |
| LVSI | 802.578 (0.001–1150.5) | 0.999 | / | / |
| D (×10−3mm2/s) | 2.063 (1.016–4.191) | 0.045 | 8.274 (2.066–33.136) | 0.003 |
| D* (×10−3mm2/s) | 1.020 (0.567–1.835) | 0.948 | / | / |
| f (%) | 0.906 (0.504–1.629) | 0.742 | / | / |
| Ktrans (min−1) | 0.487 (0.236–1.003) | 0.051 | 0.155 (0.034–0.710) | 0.016 |
| Ve | 1.008 (0.560–1.812) | 0.979 | / | / |
| Kep (min−1) | 0.501 (0.244–1.032) | 0.061 | 1.172 (0.425–3.234) | 0.759 |
[i] D = true diffusion coefficient; D* = pseudo-diffusion coefficient; f = microvascular volume fraction; FIGO = international federation of gynecology and obstetrics; CI = confidence interval; Kep = rate transfer constant; Ktrans = volume transfer constant; LVSI = lymphovascular space invasion; OR = odds ratio;. SD = standard deviation; Ve = volume of extravascular extracellular space per unit volume of tissue
[ii] The bold typeface in the table indicates the logistic regression analyses with statistical significance.
[iii] In the analysis of the high- and low-risk group, the TP53 mutant data were analysed only for these patients who had the p53 gene test. The remaining parameters, such as diameter, were analysed for all 74 patients.
FIGURE 4.
Receiver operating characteristic (ROC) curves, (A) shows each parameter and the combination of independent predictors for differentiation of TP53-mutant and TP53-wild early-stage endometrial carcinoma (EC); (B) shows each parameter and the combination of independent predictors for differentiation of low-risk and non-low-risk early-stage EC.
TABLE 5.
Predictive performance of different parameters
| Parameters | AUC (95% CI) | P-value | Cutoff | Sensitivity | Specificity | Comparison with combined diagnosis |
|---|---|---|---|---|---|---|
| Low vs non-low risk | ||||||
| D (×10−3mm2/s) | 0.761 (0.648–0.853) | < 0.001 | 0.691 | 73.33% | 72.73% | Z = 3.113, P = 0.002 |
| D* (×10−3mm2/s) | 0.536 (0.416–0.653) | 0.598 | / | / | / | / |
| f (%) | 0.688 (0.569–0.790) | 0.003 | 1.240 | 36.67% | 93.18% | Z = 4.317, P < 0.001 |
| Ktrans (min−1) | 0.852 (0.750–0.924) | < 0.001 | 0.487 | 90.00% | 68.18% | Z = 2.713, P = 0.007 |
| Ve | 0.808 (0.700–0.890) | < 0.001 | 0.401 | 83.33% | 70.45% | Z = 3.175, P = 0.002 |
| Kep (min−1) | 0.585 (0.652–0.849) | 0.204 | / | / | / | / |
| Combined diagnosis 1 | 0.947 (0.869–0.986) | < 0.001 | / | 83.33% | 93.18% | / |
| TP53 mutant vs wild | ||||||
| D (×10−3mm2/s) | 0.694 (0.541–0.821) | 0.019 | 0.605 | 92.00% | 47.62% | Z = 2.169, P = 0.030 |
| D* (×10−3mm2/s) | 0.545 (0.391–0.692) | 0.498 | / | / | / | / |
| f (%) | 0.535 (0.382–0.648) | 0.388 | / | / | / | / |
| Ktrans (min−1) | 0.679 (0.525–0.809) | 0.036 | 0.499 | 80.00% | 61.90% | Z = 2.572, P = 0.010 |
| Ve | 0.568 (0.413–0.713) | 0.675 | / | / | / | / |
| Kep (min−1) | 0.773 (0.626–0.884) | < 0.001 | 1.557 | 80.00% | 66.67% | Z = 1.272, P = 0.203 |
| Combined diagnosis 2 | 0.867 (0.734–0.949) | < 0.001 | / | 92.00% | 80.95% | / |
[i] AUC = area under the receiver operating characteristic (ROC) curve; D = true diffusion coefficient; D* = pseudo-diffusion coefficient; f = microvascular volume fraction; Kep = rate transfer constant; Ktrans = volume transfer constant; Ve = volume of extravascular extracellular space per unit volume of tissue
[ii] The combined diagnosis 1 represents f + Ktrans + Ve; the combined diagnosis 2 represents D + Ve
FIGURE 5.
In the prediction of TP53 status, receiver operating characteristic curves (A), calibration curves (B), and decision curve analysis (C) of the validation model.
FIGURE 6.
In the prediction of risk stratification, receiver operating characteristic curves (A), calibration curves (B), and decision curve analysis (C) of the validation model.