Association between high expression of phosphorylated Akt and mammalian target of rapamycin and improved survival in salivary gland adenoid cystic carcinoma

Head Neck. 2017 Jun;39(6):1145-1154. doi: 10.1002/hed.24732. Epub 2017 Feb 23.


Background: Previous genomic studies revealed phosphotidylinositol-3-kinase (PI3K)/Akt pathway mutation in human salivary gland adenoid cystic carcinoma (ACC). No validation of its prognostic value has been reported.

Methods: P-Akt, pan-Akt, phosphorylated-mammalian target of rapamycin (p-mTOR), PI3K, and insulin-like growth factor-1 receptor beta (IGF-1Rβ) were detected on 120 salivary gland ACC/adjacent salivary gland pairs immunohistochemically and were correlated with clinicopathological data.

Results: Expression of cytoplasmic and nuclear p-Akt, cytoplasmic p-mTOR, nuclear pan-Akt, and nuclear IGF-1Rβ were higher in ACC than in adjacent salivary glands. P-Akt, p-mTOR, PI3K, and IGF-1Rβ expression were correlated with one another in both cytoplasm and nucleus. Low p-mTOR expression in both subcellular compartments was associated with locoregional recurrence, poor disease-free survival (DFS), and overall survival (OS). Low nuclear p-Akt (Ser473) and p-mTOR expression were independent predictors for poor OS and DFS, respectively.

Conclusion: High level of Akt/mTOR activation in ACC is correlated with a significantly improved survival. P-mTOR and nuclear p-Akt are prognostic biomarkers of salivary gland ACC. © 2017 Wiley Periodicals, Inc. Head Neck 39: 1145-1154, 2017.

Keywords: adenoid cystic carcinoma; insulin-like growth factor-1 receptor (IGF-1R); phosphotidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR); prognostic biomarker; salivary gland cancer.

MeSH terms

  • Adult
  • Aged
  • Biopsy, Needle
  • Carcinoma, Adenoid Cystic / drug therapy
  • Carcinoma, Adenoid Cystic / genetics*
  • Carcinoma, Adenoid Cystic / mortality
  • Carcinoma, Adenoid Cystic / pathology
  • Disease-Free Survival
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Immunohistochemistry
  • Intracellular Signaling Peptides and Proteins / genetics
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Phosphorylation
  • Predictive Value of Tests
  • Proportional Hazards Models
  • Proto-Oncogene Proteins c-akt / drug effects
  • Proto-Oncogene Proteins c-akt / genetics*
  • Retrospective Studies
  • Risk Assessment
  • Salivary Gland Neoplasms / drug therapy
  • Salivary Gland Neoplasms / genetics*
  • Salivary Gland Neoplasms / mortality
  • Salivary Gland Neoplasms / pathology
  • Signal Transduction
  • Sirolimus / pharmacology
  • Survival Analysis
  • TOR Serine-Threonine Kinases / drug effects
  • TOR Serine-Threonine Kinases / genetics*


  • ANKRD28 protein, human
  • Intracellular Signaling Peptides and Proteins
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Sirolimus