Analysis of PIK3CA and Akt/protein kinase B in head and neck squamous cell carcinoma

Irina Fenic1, Klaus Steger, Christin Gruber

  • 1Department of Urology, University of Giessen, 35392 Giessen, Germany.

Oncology Reports
|June 6, 2007
PubMed

Insights

PIK3CA gene alterations, including copy number gain and mRNA overexpression, were investigated in head and neck squamous cell carcinoma (HNSCC). While mutations were absent, PIK3CA gain correlated with lymph node metastasis and mRNA expression with tumor stage, suggesting a role in HNSCC progression.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • The PIK3CA gene encodes the p110-alpha catalytic subunit of phosphatidylinositol 3-kinase (PI3K), a key signaling molecule.
  • PIK3CA is frequently altered in various cancers, playing a role in cell growth, proliferation, and survival.
  • Its involvement in head and neck squamous cell carcinoma (HNSCC) pathogenesis requires further elucidation.

Purpose of the Study:

  • To investigate the frequency of PIK3CA hot-spot mutations, copy number alterations (gain and amplification), and gene/protein expression in HNSCC.
  • To correlate these molecular findings with clinicopathological features of HNSCC.
  • To assess the relationship between PIK3CA pathway components and clinical outcomes.

Main Methods:

  • Analysis of PIK3CA hot-spot mutations in exons 9 and 20 via sequencing.
  • Quantitative assessment of PIK3CA genomic gain and amplification using techniques like qPCR or FISH.
  • Measurement of PIK3CA mRNA and p110 alpha protein expression using RT-qPCR and Western blotting, respectively.
  • Evaluation of phosphorylated-Akt (pAkt) levels as a downstream marker of PI3K pathway activation.
  • Statistical correlation of molecular data with clinicopathological parameters.

Main Results:

  • No non-synonymous PIK3CA mutations were detected in the studied HNSCC cohort.
  • PIK3CA copy number gain occurred in 36.4% and amplification in 9% of cases.
  • PIK3CA mRNA overexpression was observed in 48.5% of HNSCC samples.
  • No significant correlation was found between PIK3CA DNA copy number status and mRNA or protein expression.
  • PIK3CA copy number gain showed a direct association with lymph node metastasis (p=0.025).
  • PIK3CA mRNA expression correlated with advanced tumor stage (p=0.015).
  • A strong positive correlation existed between p110 alpha protein and pAkt expression (p<0.001).

Conclusions:

  • PIK3CA may function as an oncogene in HNSCC development.
  • Mutations and amplifications of PIK3CA appear infrequent in HNSCC.
  • Epigenetic alterations leading to PIK3CA mRNA overexpression likely contribute to HNSCC progression, particularly in advanced stages.
  • The strong correlation between p110 alpha and pAkt highlights the activation of the PI3K/Akt pathway in HNSCC.

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