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

  • Stefanie Aust
  • Katharina Auer
  • Anna Bachmayr-Heyda
  • Carsten Denkert
  • Jalid Sehouli
  • Ioana Braicu
  • Sven Mahner
  • Sandrina Lambrechts
  • Ignace Vergote
  • Christoph Grimm
  • Reinhard Horvat
  • Dan Cacsire Castillo-Tong
  • Robert Zeillinger
  • Dietmar Pils

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.

Bibliographical data

Original languageEnglish
ISSN1476-4598
DOIs
Publication statusPublished - 01.01.2014
PubMed 24655477