Tissue microarray analysis of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer patients

The goal of this study was to determine the diagnostic and prognostic potential of X-linked inhibitor of apoptosis (XIAP) expression in breast cancer. We analyzed a tissue microarray comprised of 100 breast cancer cases and 70 matched normal samples. Analysis of an online database, which included 2,977 patients, was also performed. There was a significant difference in cytoplasmic expression of XIAP (XIAP-C) between breast cancer tissue and matched normal (p<0.001). Staining of XIAP-C was defined as negative (breast cancer 8.42% vs. normal 30.91%), slight (40.0 vs. 45.45%), moderate (43.16 vs. 23.64%), or high (8.42 vs. 0%). High XIAP-C protein expression correlated with human epidermal growth factor receptor 2 (HER-2) status (p=0.010) and with human p53 mutant-type (P53) status (p=0.039). We found that XIAP expression did not correlate with disease-free survival (p=0.706) and overall survival (p=0.496) of breast cancer patients. An Internet-based system analysis confirmed our results. In the subgroup analysis, basal-like breast cancer patients with high XIAP levels in the tumor had a significantly increased risk of relapse; thus, the up-regulation of XIAP appeared to be predictive of poor relapse-free survival (p=0.013). Kaplan-Meier curves also identified a significant correlation between distant metastasis-free survival and XIAP expression in patients with lymph-node-negative disease (p=0.030). In summary, expression of XIAP-C was significantly higher in breast cancer compared to normal tissue. XIAP-C expression correlated with HER-2 status and may be considered a prognostic biomarker for basal-like breast cancer patients.