Review Article

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

Table 3

Summary of reports investigating the role of p70S6K and S6 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 polyclonal anti-p-p70S6K (Thr421/Ser424) ab (specific for p70 subunit) (SCB), diluted 1 : 250 for IHC and 1 : 200 for WB99.1% (99/111) showed nuclear stainingNo significant correlationp-p70S6K with
(i) cytoplasmic p-AKT
(ii) p-mTOR (marginal)
(iii) VEGF
No significant correlation
Yang et al. [12] (96 patients: 16 grade II, 35 III, and 45 IV)Rabbit polyclonal anti-p-S6 (Ser235/236) ab (CST), at a concentration of 0.125 Ig/mL (IHC)82.3% (79/96) cytoplasmicp-S6 with
(i) tumor grade
(ii) lower KPS score
(i) p-S6 with worse prognosis
(ii) Multivariate analysis: p-S6 as an independent prognostic factor
Li et al. [14] (87 patients: 27 grade I-II, 24 III, and 36 IV)Rabbit monoclonal anti-p-p70S6K (Thr389) ab (EP), diluted 1 : 50 (IHC)(i) 72.4% (63/87) nuclear and/or cytoplasmic
(ii) 41.7% of grade IV showed strong expression
p-p70S6K with tumor grade
McBride et al. [35] (45 patients: 22 astrocytomas grade II)(i) Rabbit polyclonal anti-p-S6 (Ser235/236) ab (SCT), diluted 1 : 200 (IHC)
(ii) Rabbit polyclonal anti-p-S6 (Ser240/244) ab (CST), diluted 1 : 200 (IHC)
(i) p-S6 (Ser235/236): 76% (29/38)
(ii) p-S6 (Ser240/244): 76% (29/38)
p-S6 (Ser235/236) with
(i) p-PRAS40
(ii) p-S6 (Ser240/244) p-S6 (Ser240/244) with
(iii) PTEN methylation
(iv) inversely PTEN expression
(i) p-S6 (Ser235/236) with OS
(ii) p-S6 (Ser240/244) with OS
Annovazzi et al. [18] (54 patients: 10 grade II, 10 III, and 34 IV)Rabbit polyclonal anti-p-S6 (Ser240/244) ab (CST), diluted 1 : 100 for IHC. Not provided for WB(i) 0%, 30%, and 82.3% in grade II, III, and IV, respectively
(ii) Nuclear in grade II and III but mainly cytoplasmic in grade IV
p-S6 with tumor grade p-S6 IHC with
(i) p-S6 WB
(ii) Ki-67
(iii) inversely with Beclin 1
No significant correlation
Ermoian et al. [36] (71 patients: 28 grade II, 17 III, and 26 IVAnti-p-S6 ab (CST)Not providedp-S6 unrelated to tumor gradeNo significant correlationNo significant correlation
Pelloski et al. [22] (268 grade IV)Anti p-p70S6K ab (CST), diluted 1 : 1000 (WB)Not providedp-p70S6K with
(i) p-ERK
(ii) p-mTOR
(iii) p-AKT
(iv) PTEN
(v) YKL-40
(i) p-p70S6K with shorter OS
(ii) Multivariate analysis: not retained as an independent prognostic factor
Riemenschneider et al. [23] (29 grade IV)(i) Mouse monoclonal anti-p-p70S6K (Thr389) ab (CST), diluted 1 : 200 (IHC)
(ii)Rabbit monoclonal anti-p-S6 (Ser235/236) ab (CST), diluted 1 : 200 (IHC)
Not provided(i) p-p70S6K
with p-AKT
(ii) p-S6 with p-AKT
Ckakravarti et al. [25] (11 grade II, 13 III, and 56 IV)Anti-p-p70S6K (Thr389) ab (CST), diluted 1 : 50 (WB)39.1% (36/92) of grade IVp-p70S6K with tumor gradep-p70S6K with
(i) p-PI3K
(ii) p-AKT
(iii) inversely cCas3
p-p70S6K with
(i) adverse outcome
(ii) reduced time to death
Multivariate analysis: p-p70S6K as an independent prognostic factor
Choe et al. [26] (45 grade IV)Anti p-S6 (Ser235/236) ab (CST), diluted 1 : 50 (IHC)Not providedp- S6 with
(i) EGFRwt
(ii) EGFRvIII
(iii) p-mTOR
(iv) p-ERK

ab: antibody, cCas3: cleaved caspase 3, CST: Cell Signaling Technology (Beverly, MA), EP: Epitomics (CA, USA), IHC: immunohistochemistry, KPS: Karnofsky Performance Status, OS: overall survival, p-ERK: phosphorylated extracellular-signal-regulated kinase, SCB: Santa Cruz Biotechnology, VEGF: vascular endothelial growth factor, WB: Western blot.