Review Article

The Clinical and Prognostic Significance of Activated AKT-mTOR Pathway in Human Astrocytomas

Table 2

Summary of reports investigating the role of mTOR activation in astrocytomas.

Report (number of cases and grades)Antibody usedImmunostaining percentageCorrelations with clinicopathological featuresOther correlationsSurvival analysis

Korkolopoulou et al. [30] (111 patients: 25 grade II, 15 III, and 71 IV)Rabbit monoclonal anti-p-mTOR (Ser2448) ab (CST), diluted 1 : 50 for IHC and 1 : 1.000 (WB)(i) 84.7% (94/111) cytoplasmic/membranous
(ii) 2.7% (3/111) nuclear
Gade III and IV marginally higher p-mTOR expression than grade IIp-mTOR with
(i) nuclear and cytoplasmic p-AKT
(ii) p-p70S6K
(iii) p-4E-BP1
(iv) VEGF
p-mTOR with worse DFS
Li et al. [14] (87 patients: 27 grade I-II, 24 III, and 36 IV)Rabbit monoclonal anti-p-mTOR (Ser2448) ab (EP), diluted 1 : 100 (IHC)(i) 74.7% (65/87) nuclear and/or cytoplasmic
(ii) 44.4% of grade IV strong expression
p-mTOR with tumor grade
Annovazzi et al. [18] (54 patients: 10 grade II, 10 III, and 34 IV)Rabbit polyclonal anti-p-mTOR (Ser2448) ab (CST), diluted 1 : 75 (IHC)0%, 70%, and 81.8% nuclear in grade II, III, and IV, respectivelyp-mTOR with tumor gradep-mTOR with
(i) p-AKT
(ii) inversely Beclin 1
No significant correlation
Pelloski et al. [22] (268 grade IV)Anti-p-mTOR (Ser2448) ab (CST), diluted 1 : 100 (IHC)Not providedp-mTOR with
(i) p-ERK
(ii) p-p70S6K
(iii) p-AKT
(iv) PTEN
(v) YKL-40
(i) p-mTOR with shorter OS
(ii) Multivariate analysis: not retained as an independent prognostic factor
Riemenschneider et al. [23] (29 grade IV)Rabbit polyclonal anti-p-mTOR (Ser2448) ab (CST), diluted 1 : 75 (IHC)Not providedNo significant correlation
Choe et al. [26] (45 grade IV)p-mTOR (Ser2481) ab (CST), diluted 1 : 50 (IHC)Not providedp-mTOR with
(i) p-AKT
(ii) p-S6
(iii)  EGFRvIII

ab: antibody, CST: Cell Signaling Technology (Beverly, MA), DFS: disease-free survival, EP: Epitomics (CA, USA), IHC: immunohistochemistry, OS: overall survival, p-ERK: phosphorylated extracellular-signal-regulated kinase, VEGF: vascular endothelial growth factor, WB: Western blot.