Metastatic Lymph Node CHIP Expression is a Potential Prognostic Marker for Resected Esophageal Squamous Cell Carcinoma Patients

Abstract

C-terminal Hsp-interacting protein (CHIP) is an HSP70 and HSP90 interacting co-chaperone and an E3 ubiquitin ligase. Previous studies have reported the role of CHIP in cancer progression by targeting protein degradation. However, its role and clinical significance in esophageal squamous cell carcinoma (ESCC) has not been elucidated. We investigated the correlation of CHIP expression and clinical outcome in a group of T3N1-3M0 surgically resected ESCCs. Tissue microarrays constructed of 234 surgically resected T3N1-3M0 ESCC primary tumors (PTs) and 163 paired metastatic lymph nodes (MLNs), and sections of 56 cancer-adjacent normal epithelial blocks were used for CHIP evaluation by immunohistochemistry. The clinical and prognostic significance of CHIP expression was analyzed statistically. The expression level of CHIP in ESCC MLNs was significantly higher than that in PTs (P < 0.001). Patients with low MLNs' CHIP expression demonstrated better overall survival than those with high CHIP expression (median, 44 vs. 17.9 months; P = 0.010). Multivariate analysis showed that the MLNs' CHIP expression level was an independent prognostic factor in ESCC (relative risk, 2.157; P = 0.028). High expression of CHIP in MLNs suggests poor prognosis for patients with resected T3N1-3M0 ESCC. The result suggests that considering the protein expression of metastatic tumors is important for prognostic prediction.