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Prognostic value of PIK3CA and phosphorylated AKT expression in ovarian cancer

Joachim Woenckhaus1, Klaus Steger, Klaus Sturm

  • 1Institute of Pathology, University of Giessen and Marburg, Giessen, Germany.

Virchows Archiv : an International Journal of Pathology
|March 23, 2007
PubMed

Insights

PIK3CA gene amplification in ovarian cancer predicts early death, but the pathway from gene to p110 alpha and AKT is complex. Nuclear pAKT may indicate better survival.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Disrupted phosphatidylinositol 3-kinase (PI3K) signaling, involving AKT, is crucial in cancer.
  • The PIK3CA gene, encoding p110 alpha, is frequently altered in ovarian cancer, suggesting its role in disease progression.

Purpose of the Study:

  • To investigate the prognostic significance of PIK3CA genetic aberrations and related protein expression in ovarian carcinomas.
  • To explore the relationship between PIK3CA alterations, PI3K/AKT pathway activation, and clinical outcomes.

Main Methods:

  • Fluorescence in situ hybridization (FISH) for genetic aberrations at the 3q26.3 locus, including PIK3CA.
  • Quantitative real-time PCR (qPCR) to assess PIK3CA amplification.
  • Immunohistochemistry (IHC) to evaluate p110 alpha, phosphorylated AKT (pAKT), and Ki-67 expression.

Main Results:

  • PIK3CA amplification and high Ki-67 index were significant predictors of early tumor-associated death.
  • p110 alpha expression correlated with 3q26.3 gain and Ki-67, but not patient survival.
  • No direct correlation was found between p110 alpha and pAKT, or between pAKT and disease outcome.

Conclusions:

  • PIK3CA amplification is a significant prognostic marker in ovarian carcinoma.
  • The PI3K/AKT pathway activation in ovarian cancer is not a simple linear process following PIK3CA gain.
  • Nuclear pAKT immunoreactivity showed a trend towards improved overall survival, warranting further investigation.

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