title: Ambivalent role of pFAK-Y397 in serous ovarian cancer--a study of the OVCAD consortium.
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.
  
  
  CONCLUSIONS
  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.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Aust
authors.forename: Katharina
authors.initials: K
authors.lastname: Auer
authors.forename: Anna
authors.initials: A
authors.lastname: Bachmayr-Heyda
authors.forename: Carsten
authors.initials: C
authors.lastname: Denkert
authors.forename: Jalid
authors.initials: J
authors.lastname: Sehouli
authors.forename: Ioana
authors.initials: I
authors.lastname: Braicu
authors.forename: Sven
authors.initials: S
authors.lastname: Mahner
authors.forename: Sandrina
authors.initials: S
authors.lastname: Lambrechts
authors.forename: Ignace
authors.initials: I
authors.lastname: Vergote
authors.forename: Christoph
authors.initials: C
authors.lastname: Grimm
authors.forename: Reinhard
authors.initials: R
authors.lastname: Horvat
authors.forename: Dan Cacsire
authors.initials: DC
authors.lastname: Castillo-Tong
authors.forename: Robert
authors.initials: R
authors.lastname: Zeillinger
authors.affiliation: Department of Obstetrics and Gynecology, Molecular Oncology Group, Comprehensive Cancer Center, Medical University of Vienna, Waehringer Guertel 18-20, Room-No,: 5,Q9,27, A-1090 Vienna, Austria. dietmar.pils@univie.ac.at.
authors.forename: Dietmar
authors.initials: D
authors.lastname: Pils
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D018572:Disease-Free Survival; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics*; D006801:Humans; D007150:Immunohistochemistry; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009375:Neoplasms, Glandular and Epithelial / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology*; D010766:Phosphorylation; D011237:Predictive Value of Tests; D011379:Prognosis; D016016:Proportional Hazards Models; D046888:Tissue Array Analysis; D059467:Transcriptome
chemical_list: D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human