title: Expression of DNA repair proteins in endometrial cancer predicts disease outcome.
abstract: OBJECTIVE
  The consequences of defective homologous recombination and other DNA repair pathways are important in disease outcomes of numerous tumor types. The objective of this study was to explore BRCA1, PARP, FANCD2, PTEN, H2AX, and ATM protein expression in endometrial cancer (EC).
  
  
  METHODS
  PARP1, γH2AX, ATM, FANCD2, PTEN, BRCA1, and p53 proteins were evaluated in EC tissue microarray (TMA) and their expressions were correlated with clinical and pathological parameters in 357 patients.
  
  
  RESULTS
  In type I EC, PARP1(+), ATM(+), and FANCD2(+) were associated with high tumor grade (p 0.031, p 0.0045, p 0.0062 respectively); γH2AX(+) and FANCD2(+) with advanced tumor stage (p 0.0004, p 0.0085 respectively); γH2AX(+), FANCD2(+) and p53(+) with the presence of lympho-vascular invasion (p 0.0004, p 0.0042, p 0.0098 respectively); and γH2AX(+) and ATM(+) with tumor recurrence (p 0.0203, p 0.0465) respectively. In type II EC, only PARP1(+) was associated with tumor stage (p 0.0499). EC patients with p53(+) or FANCD2(+) were more likely to recur with 5year recurrence free survival (RFS) probability of 71.4% in comparison to 85.5% for the other patients and they were more likely to have shorter 5year overall survival (OS) of 66.46% in comparison to 78.5% of those other patients Finally, patients with ATM(+) and p53(+) or FANCD2(+) were more likely to recur with 5year RFS probability of 68% versus 80.3% for the other patients.
  
  
  CONCLUSIONS
  DNA repair proteins seemed to play an important role in EC, and their expressions can forecast for poor outcomes.
authors: Department of Pathology at University of Southern California, Los Angeles, CA, USA. Electronic address: mhawechf@usc.edu.
authors: Paulette
authors: P
authors: Mhawech-Fauceglia
authors: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Dan
authors: D
authors: Wang
authors: Department of Pathology at University of Southern California, Los Angeles, CA, USA.
authors: Grace
authors: G
authors: Kim
authors: Department of Pathology at University of Southern California, Los Angeles, CA, USA.
authors: Maryam
authors: M
authors: Sharifian
authors: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Xiwie
authors: X
authors: Chen
authors: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Qian
authors: Q
authors: Liu
authors: Department of Gynecologic Oncology at University of Southern California, Los Angeles, CA, USA.
authors: Yvonne G
authors: YG
authors: Lin
authors: Department of Biostatistics and Bioinformatics, Roswell Park Cancer Institute, Buffalo, NY, USA.
authors: Song
authors: S
authors: Liu
authors: Department of Gynecologic Oncology, Oregon Health & Science University, Portland, OR, USA; Knight Cancer Institute, Portland, OR, USA.
authors: Tanja
authors: T
authors: Pejovic
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D064007:Ataxia Telangiectasia Mutated Proteins / Q000096:biosynthesis; D019313:BRCA1 Protein / Q000096:biosynthesis; D004260:DNA Repair; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D052236:Fanconi Anemia Complementation Group D2 Protein / Q000096:biosynthesis; D005260:Female; D006657:Histones / Q000096:biosynthesis; D006801:Humans; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000096:biosynthesis*; D051059:PTEN Phosphohydrolase / Q000096:biosynthesis; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases / Q000096:biosynthesis
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; C499905:FANCD2 protein, human; D052236:Fanconi Anemia Complementation Group D2 Protein; C468783:H2AX protein, human; D006657:Histones; D009363:Neoplasm Proteins; C499320:PARP1 protein, human; D000071137:Poly (ADP-Ribose) Polymerase-1; D011065:Poly(ADP-ribose) Polymerases; C576324:ATM protein, human; D064007:Ataxia Telangiectasia Mutated Proteins; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human
keywords: DNA repair proteins; Endometrial cancer; Immunohistochemistry; Patient outcome