Role of centromere protein H and Ki67 in relapse-free survival of patients after primary surgery for hypopharyngeal cancer.
OBJECTIVE
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.
Department of Otolaryngology-Head and Neck Surgery, Qi-Lu Hospital, Shandong University, Jinan, China.
Jun-Xi
JX
Wang
Ying-Yao
YY
Zhang
Xue-Min
XM
Yu
Tong
T
Jin
Xin-Liang
XL
Pan
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D017209:Apoptosis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000601:surgery; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics / Q000378:metabolism*; D018572:Disease-Free Survival; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000378:metabolism* / Q000601:surgery; D019394:Ki-67 Antigen / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D034741:RNA, Small Interfering; D012844:Sincalide / Q000032:analysis
C121933:CENPH protein, human; D002868:Chromosomal Proteins, Non-Histone; D019394:Ki-67 Antigen; D034741:RNA, Small Interfering; D012844:Sincalide