title: The prognostic significance of WWOX expression in patients with breast cancer and its association with the basal-like phenotype.
abstract: OBJECTIVE
  The basal-like phenotype has been found to be an independent poor prognostic factor for breast cancer. The aim of this study was to evaluate the association of WW domain-containing oxidoreductase (WWOX) expression with the basal-like subtype and clinicopathological parameters and to determine the prognostic significance of WWOX expression in patients with breast cancer.
  
  
  METHODS
  Immunohistochemical analysis of WWOX expression was performed on 267 breast carcinoma samples, and then the mean value of WWOX expression was correlated to the basal-like status and clinicopathological parameters of the samples. The prognostic value of WWOX in primary breast cancer patients was determined for disease-free survival and overall survival.
  
  
  RESULTS
  Expression of WWOX was negative in 29% of cases, and mean WWOX levels were significantly lower in basal-like breast cancers than in those of the non-basal-like subtype (P = 0.01). WWOX negativity was associated with decreased disease-free survival (DFS) (hazard ratio = 1.83; 95% CI, 1.01 to 3.28), but not with overall survival. Other tumor variables that showed a significant association with patient survival times included node status (hazard ratio = 0.38; 95% CI, 0.17 to 0.85) and breast cancer phenotype (hazard ratio = 0.36; 95% CI, 0.19 to 0.68). Multivariate regression analysis showed that lymph node involvement (hazard ratio = 0.43; 95% CI, 0.19 to 0.97) and basal-like subtype (hazard ratio = 0.33; 95% CI, 0.17 to 0.63) were also significant independent prognostic variables, and WWOX expression was of borderline significance for DFS (hazard ratio = 0.56; 95% CI, 0.31 to 1.03).
  
  
  CONCLUSIONS
  Reduced WWOX expression is associated with the basal-like subtype and a poor disease-free survival rate for breast cancer patients. Additional studies are warranted to better understand the role of WWOX expression, to further refine prognosis, and to optimize treatment in patients with basal-like breast cancer.
authors.affiliation: Department of Surgery, Shandong University School of Medicine, Jinan 250012, China. wangxiao@sdu.edu.cn
authors.forename: Xiao
authors.initials: X
authors.lastname: Wang
authors.forename: Lan
authors.initials: L
authors.lastname: Chao
authors.forename: Guohui
authors.initials: G
authors.lastname: Ma
authors.forename: Liansheng
authors.initials: L
authors.lastname: Chen
authors.forename: Yixiu
authors.initials: Y
authors.lastname: Zang
authors.forename: Jingzhong
authors.initials: J
authors.lastname: Sun
mesh_terms: D000328:Adult; D000368:Aged; D014408:Biomarkers, Tumor / Q000032:analysis*; D001943:Breast Neoplasms / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D002280:Basal Cell Carcinoma / Q000737:chemistry* / Q000235:genetics / Q000473:pathology; D015986:Confounding Factors, Epidemiologic; D018572:Disease-Free Survival; D005260:Female; D005500:Follow-Up Studies; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D009367:Neoplasm Staging; D016017:Odds Ratio; D010088:Oxidoreductases / Q000032:analysis*; D010641:Phenotype; D011237:Predictive Value of Tests; D011379:Prognosis; D018401:Sample Size; D025521:Tumor Suppressor Proteins / Q000032:analysis*; D000074584:WW Domain-Containing Oxidoreductase
chemical_list: D014408:Biomarkers, Tumor; D025521:Tumor Suppressor Proteins; D010088:Oxidoreductases; D000074584:WW Domain-Containing Oxidoreductase; C486071:WWOX protein, human
references.citation: Clin Cancer Res. 2007 Oct 15;13(20):6115-21
references.pmid: 17947476
references.citation: Int J Radiat Oncol Biol Phys. 2008 Jan 1;70(1):35-42
references.pmid: 17855007
references.citation: Br J Cancer. 2004 Aug 16;91(4):753-9
references.pmid: 15266310
references.citation: J Clin Oncol. 2006 Dec 20;24(36):5652-7
references.pmid: 17116942
references.citation: Clin Cancer Res. 2004 Apr 1;10(7):2459-65
references.pmid: 15073125
references.citation: J Clin Oncol. 2008 May 20;26(15):2568-81
references.pmid: 18487574
references.citation: Cancer Res. 2003 Feb 15;63(4):878-81
references.pmid: 12591741
references.citation: BMC Cancer. 2005 Jun 27;5:64
references.pmid: 15982416
references.citation: Cancer. 2007 Jan 1;109(1):25-32
references.pmid: 17146782
references.citation: Int J Radiat Oncol Biol Phys. 2008 Nov 15;72(4):1056-63
references.pmid: 18676094
references.citation: Breast Cancer Res. 2007;9(5):R65
references.pmid: 17910759
references.citation: Cancer. 1989 Nov 1;64(9):1914-21
references.pmid: 2551477
references.citation: Proc Natl Acad Sci U S A. 2003 Jul 8;100(14):8418-23
references.pmid: 12829800
references.citation: Mod Pathol. 2006 Feb;19(2):264-71
references.pmid: 16341146
references.citation: Clin Cancer Res. 2004 May 1;10(9):3053-8
references.pmid: 15131042
references.citation: Arch Pathol Lab Med. 1997 Jun;121(6):578-84
references.pmid: 9199622
references.citation: Nature. 2000 Aug 17;406(6797):747-52
references.pmid: 10963602
references.citation: Cancer. 2004 Apr 15;100(8):1605-14
references.pmid: 15073846
references.citation: Eur J Clin Invest. 2008 Jun;38(6):438-46
references.pmid: 18452545
references.citation: Clin Cancer Res. 2004 Aug 15;10(16):5367-74
references.pmid: 15328174
references.citation: Int J Radiat Oncol Biol Phys. 2000 Jul 15;47(5):1169-76
references.pmid: 10889369
references.citation: Oncogene. 2005 Feb 24;24(9):1625-33
references.pmid: 15674328
references.citation: Cancer Res. 2001 Nov 15;61(22):8068-73
references.pmid: 11719429
references.citation: Clin Cancer Res. 2007 Jan 1;13(1):268-74
references.pmid: 17200365
references.citation: Breast Cancer Res. 2002;4(2):65-9
references.pmid: 11879566
references.citation: Breast Cancer Res Treat. 2005 Jan;89(2):99-105
references.pmid: 15692750
references.citation: Clin Cancer Res. 2008 Mar 1;14(5):1368-76
references.pmid: 18316557
references.citation: Proc Natl Acad Sci U S A. 2001 Sep 25;98(20):11417-22
references.pmid: 11572989
references.citation: Cancer Res. 2002 Apr 15;62(8):2258-60
references.pmid: 11956080
references.citation: Am J Surg Pathol. 2001 Mar;25(3):331-7
references.pmid: 11224603
references.citation: Cancer Res. 2000 Apr 15;60(8):2140-5
references.pmid: 10786676