The prognostic significance of WWOX expression in patients with breast cancer and its association with the basal-like phenotype.

PURPOSE: 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.

Elevated expression of phosphorylated c-Jun NH2-terminal kinase in basal-like and "triple-negative" breast cancers.

Basal-like carcinomas and human epidermal growth factor receptor 2 (HER-2/neu) overexpression carcinomas are the subgroups of breast cancers that have the most aggressive clinical behavior. Phosphorylation/activation of c-Jun NH2-terminal kinase is characterized as a stress-activated protein kinase, which regulates apoptosis after cellular stress. The aim of this study was to evaluate the association of phosphorylated c-Jun NH2-terminal kinase expression with phenotypes and clinicopathologic parameters of breast cancer. Phosphorylated c-Jun NH2-terminal kinase was immunohistochemically measured in a cohort of 160 patients with invasive breast cancer treated with therapeutic surgery followed by anthracycline or docetaxel-based chemotherapy. These results were further correlated with the phenotypes and clinicopathologic characteristics of breast cancers. Increased phosphorylated c-Jun NH2-terminal kinase expression was significantly associated with lack of estrogen receptor expression (P < .0001), positivity for cytokeratins 5/6 (P = .029), epidermal growth factor receptor (P = .035), basal-like phenotype (P = .015), and "triple-negative" phenotype (P = .01). Furthermore, the positive expression of phosphorylated c-Jun NH2-terminal kinase was positively correlated with p-glycoprotein (r = 0.54, P < .0001) and multidrug resistance-associated protein 1(r = 0.38, P < .0001) but not with lung resistance protein (r = -0.02, P = .78). Our results indicate that the activation of phosphorylated c-Jun NH2-terminal kinase may play a role in the carcinogenesis of basal-like and triple-negative breast carcinoma.