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Role of Centromere Protein H and Ki67 in Relapse-free Survival of Patients after Primary Surgery for Hypopharyngeal Cancer

  • Wang, Jun-Xi (Department of Otolaryngology-Head and Neck Surgery, Qi-Lu Hospital, Shandong University) ;
  • Zhang, Ying-Yao (Department of Otolaryngology-Head and Neck Surgery, Qi-Lu Hospital, Shandong University) ;
  • Yu, Xue-Min (Department of Otolaryngology-Head and Neck Surgery, Qi-Lu Hospital, Shandong University) ;
  • Jin, Tong (Department of Otolaryngology-Head and Neck Surgery, Qi-Lu Hospital, Shandong University) ;
  • Pan, Xin-Liang (Department of Otolaryngology-Head and Neck Surgery, Qi-Lu Hospital, Shandong University)
  • Published : 2012.03.31

Abstract

Purpose: Centromere protein H (CENP-H) and Ki67 are overexpressed in some malignancies, but whether they are predictors of survival after primary resection for hypopharyngeal squamous cell carcinoma (HSCC) remains unknown. Methods: We assessed immunohistochemical expression of CENP-H and Ki67 in 112 HSCC specimens collected between March 2003 and March 2005 for analysis by clinical characteristics. The Kaplan-Meier method was used to analyze relapse-free survival and logistic multivariate regression to determine risk factors of relapse-free survival. Cholecystokinin octapeptide assays and flow cytometry were used to examine cell proliferation and apoptosis after siRNA inhibition of CENP-H in HSCC cells. Results: Overall, 50 (44.6%) HSCC specimens showed upregulated CENP-H expression and 69 (61.6%) upregulated Ki67. An increased CENP-H protein level was associated with advanced cancer stage and alcohol history (P=0.012 and P=0.048, respectively) but an increased Ki67 protein level only with advanced cancer stage (P=0.021). Increased CENP-H or Ki67 were associated with short relapse-free survival (P<0.001 or P=0.009, respectively) and were independent predictors of relapse-free survival (P=0.001 and P=0.018, respectively). siRNA knockdown of CENP-H mRNA inhibited cell proliferation and promoted cancer cell apoptosis in vitro. Conclusions: Upregulated CENP-H and Ki67 levels are significantly associated with short relapse-free survival in HSCC. These factors may be predictors of a relapsing phenotype in HSSC cases.

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