Telomerase activity in stage II colorectal carcinoma - Telomerase-negative tumors are correlated with poor prognosis

被引:23
作者
Kawanishi-Tabata, R
Lopez, F
Fratantonio, S
Kim, N
Goldblum, J
Tubbs, R
Elson, P
Lavery, I
Bukowski, RM
Ganapathi, R
Ganapathi, MK
机构
[1] Cleveland Clin Fdn, Taussig Canc Ctr, Expt Therapeut Program, Cleveland, OH 44195 USA
[2] Cleveland Clin Fdn, Dept Colorectal Surg, Cleveland, OH 44195 USA
[3] Cleveland Clin Fdn, Dept Pathol, Cleveland, OH 44195 USA
[4] DiaDexus Inc, San Francisco, CA USA
关键词
telomerase activity; colorectal carcinoma; prognosis; disease-free survival;
D O I
10.1002/cncr.10911
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
BACKGROUND. Telomerase is a ribonucleoprotein polymerase that adds telomeric repeats to chromosome ends. This enzyme is deficient in the majority of normal somatic cells, but often is reactivated during tumorigenesis. In the current study, the authors examined telomerase activity in human American Joint Committee on Cancer Stage II colorectal carcinomas and correlated it with traditional prognostic indicators and disease outcome. METHODS. The telomerase repeat amplification protocol (TRAP) was employed to determine telomerase activity in 122 surgical specimens (from 77 male and 45 female patients) of human Stage II colorectal carcinoma. The primary site of the tumor was the colon in 52 cases and the rectum in 70 cases. Telomerase activity was correlated with traditional prognostic indicators such as gender, age, T classification, tumor size, tumor grade, and disease outcome (overall survival and disease-free survival). The Median follow-up for patients who still were alive was 5.8 years. RESULTS. Telomerase activity was detected in 80% of the tumors (98 of 122 tumors). Telomerase-positive patients differed from telomerase-negative patients in that they tended to be female (41% vs. 21%; P = 0.1), presented with primary tumors of the colon more frequently, (49% vs. 17%; P = 0.01), and had a higher T classification (T-4) (62% vs. 38%; P = 0.04). Univariate and multivariate analyses demonstrated a correlation between telomerase activity and disease-free survival (P = 0.05). CONCLUSIONS. Although a large percentage of Stage II colorectal carcinoma samples were positive for telomerase activity, the prognosis for patients with telomerase-negative tumors was found to be worse than that for patients with telomerase-positive tumors.
引用
收藏
页码:1834 / 1839
页数:6
相关论文
共 31 条
[1]  
BAKER SJ, 1990, CANCER RES, V50, P7717
[2]  
Bechter OE, 1998, CANCER RES, V58, P4918
[3]  
Bitisik O, 2000, RES COMMUN MOL PATH, V107, P3
[4]   STRUCTURE AND FUNCTION OF TELOMERES [J].
BLACKBURN, EH .
NATURE, 1991, 350 (6319) :569-573
[5]   TELOMERE ELONGATION IN IMMORTAL HUMAN-CELLS WITHOUT DETECTABLE TELOMERASE ACTIVITY [J].
BRYAN, TM ;
ENGLEZOU, A ;
GUPTA, J ;
BACCHETTI, S ;
REDDEL, RR .
EMBO JOURNAL, 1995, 14 (17) :4240-4248
[6]  
CHADENEAU C, 1995, CANCER RES, V55, P2533
[7]   p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis [J].
Chin, L ;
Artandi, SE ;
Shen, Q ;
Tam, A ;
Lee, SL ;
Gottlieb, GJ ;
Greider, CW ;
DePinho, RA .
CELL, 1999, 97 (04) :527-538
[8]   Telomerase activity and survival of patients with node-positive breast cancer [J].
Clark, GM ;
Osborne, CK ;
Levitt, D ;
Wu, F ;
Kim, NW .
JOURNAL OF THE NATIONAL CANCER INSTITUTE, 1997, 89 (24) :1874-1881
[9]   TELOMERE SHORTENING ASSOCIATED WITH CHROMOSOME INSTABILITY IS ARRESTED IN IMMORTAL CELLS WHICH EXPRESS TELOMERASE ACTIVITY [J].
COUNTER, CM ;
AVILION, AA ;
LEFEUVRE, CE ;
STEWART, NG ;
GREIDER, CW ;
HARLEY, CB ;
BACCHETTI, S .
EMBO JOURNAL, 1992, 11 (05) :1921-1929
[10]   A GENETIC MODEL FOR COLORECTAL TUMORIGENESIS [J].
FEARON, ER ;
VOGELSTEIN, B .
CELL, 1990, 61 (05) :759-767