Reduced expression of Raf-1 kinase inhibitory protein predicts regional lymph node metastasis and shorter survival in esophageal squamous cell carcinoma

Raf-1 kinase inhibitory protein (RKIP), a suppressor of metastasis, is associated inversely with the progression and metastasis of human malignancies. The present study evaluated relationships between RKIP expression and metastatic potential, clinicopathological characteristics and patient outcome in esophageal squamous cell carcinoma (ESCC). We examined tissue specimens from 138 patients with thoracic ESCC. Using immunohistochemistry, RKIP expression was detected in ESCC in situ, primary ESCC and nodal metastatic ESCC. RKIP expression was reduced in 28.9% (13/45) of ESCC in situ, in 50.0% (69/138) of primary ESCC and in 71.4% (65/91) of nodal metastatic ESCC. These levels of RKIP down-regulation differed significantly. RKIP expression was associated inversely with histological grade (P = 0.008), pathological T stage (P = 0.044), lymphatic invasion (P = 0.019), regional lymph node metastasis (LNM; P = 0.002) and stage (P = 0.041). Pathological T stage (P = 0.001), lymphatic invasion (P < 0.001) and reduced RKIP expression (P = 0.039) were independent predictors of regional LNM in ESCC. In addition, the postoperative survival of patients with RKIP-reduced ESCC was significantly shorter than for patients with RKIP-positive ESCC (P = 0.004). Reduced RKIP expression in ESCC correlated with advanced disease, regional LNM and poor prognosis. RKIP expression may serve as a novel clinical biomarker in patients with ESCC.