The X-linked inhibitor of apoptosis protein is an independent prognostic marker for rectal adenocarcinoma after preoperative chemoradiotherapy

Rectal cancer (RC) is a common malignancy of the gastrointestinal tract. Preoperative neoadjuvant concurrent chemoradiotherapy (CCRT) is considered an effective treatment as it down-stages advanced RC. X-linked inhibitor of apoptosis protein (XIAP) and survivin participate in the regulation of apoptosis, a key process in carcinogenesis and tumor progression. However, the prognostic value of concomitant expression of XIAP and survivin in RC patients undergoing neoadjuvant CCRT is not well established. Expression of XIAP and survivin proteins was evaluated by immunohistochemical staining of pre-CCRT and post-CCRT specimens of 58 rectal cancer patients. Clinicopathological parameters were also analyzed. In pre-CCRT biopsy specimens, high survivin expression was significantly associated with perineural invasion (p = 0.025), metastatic status (p = 0.015), and advanced disease stage (I-IV, p = 0.025; early vs. late, p = 0.047). In post-CCRT surgical specimens, high XIAP expression was significantly associated with age (p = 0.037), T stage (p = 0.025), disease stage (p = 0.019), and tumor regression grade (TRG) (p = 0.000). High survivin expression was significantly correlated with T stage (p = 0.044), N stage (p = 0.028), metastasis (p = 0.007), disease stage (p = 0.001), and TRG (p = 0.033). Pearson correlation calculations showed a positive correlation between XIAP and survivin immunoreactivity (p = 0.000). Patients with low XIAP and low survivin expression tended to have significantly longer overall survival (p = 0.006 and 0.001, respectively). In multivariable Cox regression analysis, patients with high XIAP, perineural invasion, and advanced stage had significantly shorter overall survival (p = 0.000, 0.002 and 0.000, respectively). In conclusion, high expression of XIAP and survivin is associated with advanced stage and poor prognosis. Expression of XIAP is positively correlated with that of survivin. These data suggest that XIAP is an independent prognostic marker and might be considered as therapy target for rectal cancer after neoadjuvant therapy.