Table 2.
The mTOR protein content in papillary thyroid cancer.
| Study | Country | Clinical Data | Method and Sample |
Results |
|---|---|---|---|---|
| Faustino et al. 2012 [51] |
Portugal | 22 FVPCT; 60 cPCT (23 (38.3%) with BRAF V600E mutation); 21 cPCT metastases; 34 HC Male/Female: no data Age: no data TNM stage: no data |
IHC, PCR tissue |
- Enhanced expression of mTOR and phosphorylated mTOR (pmTOR) Ser2448 was detected in FVPTC and cPTC, when compared with normal thyroid tissue (p ≤ 0.0001 to 0.0022). - Total mTOR expression was significantly higher in cPTC, relative to the other carcinoma histotypes (p ≤ 0.0001 to 0.0022). - The levels of pmTOR in cPTC were significantly higher than in FVPTC and cPTC metastases (p = 0.0108 and p = 0.0005, respectively). - Raptor and rictor were overexpressed (p ≤ 0.0001 to 0.0007) in TC in comparison to HC. - A significant increase in the expression of mTORC1 downstream targets relative to normal thyroid tissue, was observed only in cPTC samples (p = 0.0180 and p < 0.0001, respectively). - Higher expression of mTOR (p < 0.0001), pmTOR (p = 0.0005), and p4EBP1 Thr37/46 (p = 0.0011) was found in primary cPTC than in cPTC metastases. - Significantly higher expression of mTOR (p < 0.0001), pmTOR Ser2448 (p < 0.0001), raptor (p = 0.0037), rictor (p = 0.0323) in cPTC BRAF V600E was found than in cPTC BRAF V600E WT. |
| Ahmed et al. 2014 [53] |
Saudi Arabia | 536 PCT; 73 FVPCT; 412 cPCT; 19 TV PCT Male/Female: 141 (28)/363 (72) Age: ≤45 y 294 (58.3); >45 y 210 (41.7) TNM stage: I 304 (61.5), II 25 (5.1), III 44 (8.9), IV 121 (24.5) |
tissue microarray, IHC tissue |
- Co-expression of mTORC2 and mTORC1 activity was seen in a 32.5% (164/504) of the PTC studied and this association was statistically significant (p = 0.0244). - The p-mTORC1 expression showed a significant association with the early stage (p = 0.0286). - High expression 81.7%; low expression 18.3% |
| Tavares et al. 2016 [52] |
Portugal | 191 PCT; 119 cPTC; 47 FVPCT; 20 Other Male/Female: 35 (18)/155 (82) Age: < 45 y 99 (53), ≥ 45 y 87 (47) TNM stage: I 66 (62), II 6 (6), III 25 (23), IV 10 (9) |
PCR, IHC tissue |
- Higher pmTOR expression was associated with absence of a tumor capsule (p = 0.01), presence of distant metastases (p = 0.05), persistence of disease (one-year disease-free status and disease-free status at the end of follow-up) (p = 0.05), and NRAS mutation (p = 0.04). - Positive pmTOR expression showed to be an independent risk factor for distant metastases (odds ratio = 18.2; 95% confidence interval 2.1–157.9; p = 0.01). - Higher pmTOR expression was also correlated with a greater number of 131I therapies (r(102)-0.2, p = 0.02), greater cumulative dose of RAI (r(100)-0.3, p = 0.01), and a lesser expression of sodium iodine symporter (r(44)-0.3, p = 0.03). |
| Duman et al. 2014 [54] |
Turkey | 101 DTC; 82 (81.2%) PCT Male/Female: PCT: 16 (19.5)/66 (80.5%) Age: 45.32 ± 12.7 TNM stage: I: 56 (68.3%); II: 19 (23.2%); III: 3 (4.9%); IV: 2 (3.7%) |
PCR, WES tissue |
- No significant association between mTOR and tumor size (p = 0.818) - No statistically significant correlation was found between mTOR expression and lymph vascular invasion, capsular invasion, or multifocality (p = 0.392, p = 0.65 and p = 0.156, respectively). |
Abbreviations: mammalian target of rapamycin (mTOR), papillary thyroid cancer (PTC), differentiated thyroid cancer (DTC), healthy controls (HC), follicular variants of PTC (FVPTC), classic PTC (cPTC), tall cell variant papillary thyroid cancer (TCV PTC), polymerase chain reaction (PCR), immunohistochemistry (IHC).