Table 2. Characteristic of the studies included in the comparative analysis.
| Gene Expression Classifier (GEC) |
Mutation/Fusion panel | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| Test-methods to Select Thy-3 nodules for surgery | GAL-3-ICC | BRAF Mutation Analysis |
GEC (Veracyte Afirma®) |
GEC + BRAF (Veracyte Afirma® + BRAF) | Mutation/Fusion panel (Asuragen miRInform™, Quest Diagnostic & Interpace Diagnostic ThyGenX®) | Mutation/Fusion panel + miRNA GEC (Interpace Diagnostic ThyGenX®/ ThyraMIR™) |
Mutation/ Fusion panel by NGS (Thyroseq Ver. 2.0) |
FDG- PET/CT |
MIBI-Scan | TSHR mRNA Assay |
| Bio-molecular Marker Type | Protein (Galectin-3) |
DNA (1 gene, 1 codon) | RNAs (167 genes) | RNAs & DNAs (167 genes) + BRAF mutation | RNAs and DNAs (4 genes, 14 SNPs and 3 chromosome rearrangements) | RNAs and DNAs (4 genes, 14 SNPs & 3 chromosome rearrangements) + 10 miRNA | RNAs & DNAs (13 genes and 42 gene fusions) | Glucose uptake |
Sesta-MIBI uptake |
TSHR mRNA |
| Method | Immuno- CytoChemistry |
BRAF (V600E) mutation analysis |
Gene Expression Classifier | Gene Expression Classifier + BRAF (V600E) mutation analysis | RT-PCR, Fluorescence Melting Curve, Luminex, Sanger sequencing, Pyrosequencing | RT - qPCR Luminex | Next Generation Sequence (NGS) | FDG- PET/CT |
Thyroid Scintigraphy (visual analysis) | qRT -PCR Blood Assay |
| Patients and samples recruitment | Pooled from 9 studies | Pooled from 24 studies | Multicenter (49, USA) | Multicenter (USA, Denmark, Italy) Pooled from 8 studies | Multicenter (USA) | 1 Center (USA) |
Pooled from 3 studies (Italy) |
Pooled from 2 studies (USA) | ||
| Laboratory for Testing | 9 Centers (Europe and Chile) |
24 Centers (Europe, Canada, USA, China, Korea) | 1 Center (USA) |
1 Center (USA) | 1 Center (USA) |
3 Centers (Italy) | 1 Center (USA) |
|||
| Total number of cases | 1,266 | 2,625 | 210 | 165 | 1,141 | 109 | 143 | 51 | 217 | 114 |
|
Cancer Prevalence (%) (95% CI) |
33 (30.9-36.2) |
45 (42.8-46.6) |
24 (18.6-30.7) |
27 (20.0-34.1) |
24 (21.7-26.7) |
32 (23.5-41.7) |
27 (20.2-35.3) |
20 (9.82-33.1) |
29 (23.1-35.6) |
44 (34.6-53.5) |
| True Positive (TP) eqv. with hit | 351 (27.7%) |
474 (18.1%) |
46 (21.9%) |
39 (23.6%) |
141 (12.4%) |
31 (28.4%) |
35 (24.5%) |
8 (15.7%) |
42 (19.4%) |
35 (30.7%) |
| True Negative (TN) eqv. with correct rejection | 716 (56.6%) |
1,451 (55.3%) |
82 (39.0%) |
60 (36.4%) |
805 (70.6%) |
63 (57.8%) |
97 (67.8%) |
25 (49.0%) |
129 (59.4%) |
52 (45.6%) |
| False Positive (FP) eqv. with false alarm | 127 (10.0%) |
4 (0.1%) |
77 (36.7%) |
61 (37.0%) |
61 (5.3%) |
11 (10.1%) |
7 (4.9%) |
16 (31.4%) |
25 (11.5%) |
12 (10.5%) |
| False Negative (FN) eqv. with miss | 72 (5.7%) |
696 (26.5%) |
5 (2.4%) |
5 (3.0%) |
134 (11.7%) |
4 (3.7%) |
4 (2.8%) |
2 (3.9%) | 21 (9.7%) |
15 (13.2%) |
| Reference | [43, 78, 80-86] | [46, 51-53, 56-58, 63-79] | [60] | [61] | [51-58] | [54] | [59] | [62] | [34, 35, 46] | [32, 50] |
Comparison of the seven different test-methods and their variants, proposed for the same diagnostic purpose in thyroid nodules with indeterminate cytology. The type of bio- molecular marker, the method used, the total number of cases examined and the type of the study are also indicated. For each test-method the cancer prevalence, with 95% CI, and the results are reported.