Clinical outcomes and differential effects of PI3K pathway mutation in obese versus non-obese patients with cervical cancer

Perry Grigsby, Adnan Elhammali, Fiona Ruiz, Stephanie Markovina, Michael D. McLellan, Christopher A. Miller, Anupama Chundury, Ngoc Anh L. Ta, Ramachandran Rashmi, John D. Pfeifer, Robert S. Fulton, Todd DeWees, Julie K. Schwarz

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

The purpose of this study was to evaluate the effect of obesity and obesityassociated factors on the outcomes of patients with cervical cancer. Outcomes were evaluated in 591 patients with FIGO Ib to IV cervical cancer treated uniformly with definitive radiation. Patients were stratified into 3 groups based upon pretreatment Body Mass Index (BMI): A ≤ 18.5; B 18.6 - 34.9; and C ≥ 35. The 5-year freedom from failure rates were 58, 59, and 73% for BMI groups A, B, and C (p = 0.01). Overall survival rates were 50, 59, and 68%, respectively (p = 0.02). High expression of phosphorylated AKT (pAKT) was associated with poor outcomes only in non-obese patients. Obese patients with PI3K pathway mutant tumors had a trend toward favorable outcomes, while a similar effect was not observed in non-obese patients. Compared to similar tumors from non-obese hosts, PIK3CA and PTEN mutant tumors from obese patients failed to express high levels of phosphorylated AKT and its downstream targets. These results show that patients with obesity at the time of diagnosis of cervical cancer exhibit improved outcomes after radiation. PI3K/AKT pathway mutations are common in obese patients, but are not associated with activation of AKT signaling.

Original languageEnglish (US)
Pages (from-to)4061-4073
Number of pages13
JournalOncotarget
Volume9
Issue number3
DOIs
StatePublished - 2018

Keywords

  • Cervical cancer
  • Mutation
  • Obesity
  • PI3K
  • PTEN

ASJC Scopus subject areas

  • Oncology

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    Grigsby, P., Elhammali, A., Ruiz, F., Markovina, S., McLellan, M. D., Miller, C. A., Chundury, A., Ta, N. A. L., Rashmi, R., Pfeifer, J. D., Fulton, R. S., DeWees, T., & Schwarz, J. K. (2018). Clinical outcomes and differential effects of PI3K pathway mutation in obese versus non-obese patients with cervical cancer. Oncotarget, 9(3), 4061-4073. https://doi.org/10.18632/oncotarget.23664