Genetic alterations of PIK3CA and tumor response in patients with locally advanced cervical squamous cell carcinoma treated with cisplatin-based concurrent chemoradiotherapy

Exp Mol Pathol. 2015 Jun;98(3):407-10. doi: 10.1016/j.yexmp.2015.03.014. Epub 2015 Mar 13.

Abstract

Objective: The objective of this study was to investigate the predictive value of common genetic alterations of PI3K/AKT/mTOR and Ras/Raf/MAPK pathways in patients with locally advanced cervical squamous cell carcinoma (LACSCC) treated with cisplatin-based concurrent chemoradiotherapy (CCRT).

Methods: Patients with LACSCC, treated at a single institution with CCRT were eligible for this retrospective study. A total of sixty pre-treatment tumor biopsies were retrieved. Somatic mutations were detected by pyrosequencing and CNV was determined by quantitative realtime PCR. The association of genetic alterations with clinicopathological characteristics and treatment response were analyzed.

Results: Patients without genetic alterations (mutations or amplification) of PIK3CA had a significantly higher response rate than patients with these alterations (p=0.006). In the logistic regression analysis, PIK3CA genetic alterations retained an independent factor in predicting response to CCRT.

Conclusions: Somatic mutations and copy number amplification of PIK3CA were associated with response to CCRT in patients with cervical squamous cell carcinoma.

Keywords: Cervical carcinoma; Chemoradiotherapy; Genetic alterations; PIK3CA; Response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Carcinoma, Squamous Cell / genetics*
  • Carcinoma, Squamous Cell / therapy
  • Chemoradiotherapy*
  • Cisplatin / therapeutic use
  • Class I Phosphatidylinositol 3-Kinases
  • DNA Copy Number Variations*
  • Female
  • Humans
  • Middle Aged
  • Mutation*
  • Phosphatidylinositol 3-Kinases / genetics*
  • Treatment Outcome
  • Uterine Cervical Neoplasms / genetics*
  • Uterine Cervical Neoplasms / therapy

Substances

  • Antineoplastic Agents
  • Phosphatidylinositol 3-Kinases
  • Class I Phosphatidylinositol 3-Kinases
  • PIK3CA protein, human
  • Cisplatin