Overexpression of Raf-1 and ERK1/2 in sacral chordoma and association with tumor recurrence

摘要

Chordoma is a rare and low-malignant neoplasm which is considered to arise from notochord remnants. Due to its large resistance to chemotherapy and radiotherapy, surgical resection so far is the prior treatment for chordoma. However, the recurrence rate is high even after complete surgical resection. Recently, targeted cancer therapy has been demonstrated to be effective in several other tumors, while the related research on chordoma is rare. Mitogen-activated protein kinase signaling pathway is acknowledged to participate in tumor development, in which Raf-1 and extracellular regulated protein kinase 1/2 (ERK1/2) play vital roles. In this study, we evaluated the expression of Raf-1 and ERK1/2 by immunohistochemical staining in 42 chordoma tissue and 16 distant normal tissue. Moreover, we also investigated the correlations of Raf-1 and ERK1/2 expression with clinical features in sacral chordoma. Expression of Raf-1 and ERK1/2 was both significantly higher in sacral chordoma tissue than distant normal tissue (P = 0.008, P = 0.019). Raf-1 positive expression was related to surrounding muscle invasion (P = 0.032) and chordoma recurrence (P = 0.002), but the results did not indicate any association with patients’ age, gender, tumor size and location. ERK1/2 was associated with tumor size (P = 0.044) instead of other clinical factors (P > 0.05). Spearman correlation test showed close relation between ERK1/2 and Raf-1 (P = 0.001, r = 0.518). Kaplan–Meier survival Curve and log-rank test showed that Raf-1 positive expression was associated with shorter continuous disease-free survival time (CDFS) (P = 0.001), while ERK1/2 had no relation to CDFS (P = 0.961). Conclusively, Raf-1 may be an important biomarker in predicting the prognosis of chordoma patients.