The prognostic significance of WWOX expression in patients with breast cancer and its association with the basal-like phenotype
- 120 Downloads
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.
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.
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).
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.
KeywordsBreast cancer Gene WWOX Basal-like phenotype CK5/6 EGFR
This work supported, in whole or in part, by grants from Shandong Province Natural Science Foundation (No. Y2006C30), Shandong Health and Medicine Founds, China Postdoctoral Foundation (No.20090461225, 20090461226), Doctor Funds of Shandong Province (No. BS2009SW031), and Science and Technology Development Plan of Jinan, China (No. 061033-2).
Conflict of interest statement
- Le Doussal V, Tubiana-Hulin M, Friedman S, Hacene K, Spyratos F, Brunet M (1989) Prognostic value of histologic grade nuclear components of Scarff-Bloom-Richardson (SBR): an improved score modification based on a multivariate analysis of 1262 invasive ductal breast carcinomas. Cancer 64(9):1914–1921CrossRefPubMedGoogle Scholar
- Parikh RR, Housman D, Qifeng Y, Toppmeyer D, Wilson LD, Haffty BG (2008a) Prognostic value of triple-negative phenotype at the time of locally recurrent, conservatively treated breast cancer. Int J Radiat Oncol Biol Phys 72(4):1–8Google Scholar
- Turner BC, Gumbs AA, Carter D, Glazer PM, Haffty BG (2004) Cyclin D1 expression and early breast cancer recurrence following lumpectomy and radiation. Int J Radiat Oncol Biol Phys 47(5):1169–1176Google Scholar