Ambivalent role of pFAK-Y397 in serous ovarian cancer--a study of the OVCAD consortium

Mol Cancer. 2014 Mar 21:13:67. doi: 10.1186/1476-4598-13-67.

Abstract

Background: Focal adhesion kinase (FAK) autophosphorylation seems to be a potential therapeutic target but little is known about the role and prognostic value of FAK and pFAK in epithelial ovarian cancer (EOC). Recently, we validated a gene signature classifying EOC patients into two subclasses and revealing genes of the focal adhesion pathway as significantly deregulated.

Methods: FAK expression and pFAK-Y397 abundance were elucidated by immunohistochemistry and microarray analysis in 179 serous EOC patients. In particular the prognostic value of phosphorylated FAK (pFAK-Y397) and FAK in advanced stage EOC was investigated.

Results: Multiple Cox-regression analysis showed that high pFAK abundance was associated with improved overall survival (HR 0.54; p = 0.034). FAK was positive in a total of 92.2% (n = 165) and high pFAK abundance was found in 36.9% (n = 66). High pFAK abundance (36.9% ; n = 66) was associated with either nodal positivity and/or distant metastasis (p = 0.030). Whole genome gene expression data revealed a connection of the FAK-pFAK-Y397 axis and the mTOR-S6K1 pathway, shown to play a major role in carcinogenesis.

Conclusion: The role of pFAK-Y397 remains controversial: although high pFAK-Y397 abundance is associated with distant and lymph node metastases, it is independently associated with improved overall survival.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Carcinoma, Ovarian Epithelial
  • Disease-Free Survival
  • Female
  • Focal Adhesion Kinase 1 / genetics*
  • Humans
  • Immunohistochemistry
  • Kaplan-Meier Estimate
  • Middle Aged
  • Neoplasms, Glandular and Epithelial / genetics*
  • Neoplasms, Glandular and Epithelial / mortality
  • Neoplasms, Glandular and Epithelial / pathology*
  • Oligonucleotide Array Sequence Analysis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / mortality
  • Ovarian Neoplasms / pathology*
  • Phosphorylation
  • Predictive Value of Tests
  • Prognosis
  • Proportional Hazards Models
  • Tissue Array Analysis
  • Transcriptome

Substances

  • Focal Adhesion Kinase 1
  • PTK2 protein, human