[Prognostic value of thymidylate synthase, topoisomerase-1 and Ki-67 in advanced colorectal cancer patients on irinotecan and fluorouracil treatment].
OBJECTIVE
To investigate the prognostic value of thymidylate synthase (TS), topoisomerase-1 (Topo-1), and proliferating index Ki-67 in advanced colorectal cancer patients on irinotecan (CPT-11) in combination with fluorouracil treatment (5-Fu).


METHODS
The biomarker expression of TS, Topo-1 and Ki-67 in 78 patients detected immunohistochemically were correlated with the clinical outcome.


RESULTS
The expressions of those biomarkers were not correlated with clinical therapeutic response, but with time to progression (TTP) and/or overall survival (OS). Patients with low expression of TS had significantly longer TTP (P < 0.05) and in OS (P < 0.05). The low expression of Ki-67 was also significantly predictive of longer survival (P < 0.05). As compared with any biomarker, the combination of any two biomarkers still possessed no predictive value to therapeutic response, but an enhanced predictive value to prognosis. The median time to progression in patients with low expression of TS, or Ki-67, or both were 9, 8 and 17 months, respectively; in patients with low expression of TS, or Topo-1, or both were 9, 9 and 13 months; in patients with low expression of Topo-1, or Ki-67, or both were 8, 9 and 11 months. TTP was significantly longer in patients with low expression of two biomarkers as compared with those with high expression (P = 0.031).


CONCLUSIONS
TS, Topo-1, and Ki-67 are not predictive for chemotherapy response to CPT-11 combined with 5-Fu, but valuable in predicting prognosis. The combination of any two biomarkers can provide more powerful prognostic information for advanced colorectal cancer patients.
Xu
Jian-ming
JM
Cancer Center, Beijing 307 Hospital, Beijing 100039, China. jmxu2003@yahoo.com
Zhu
Bu-dong
BD
Mangia
Anita
A
Simone
Gianni
G
Montemurro
Severino
S
Giuliani
Francesco
F
Maiello
Evaristo
E
Colucci
Giuseppe
G
Paradiso
Angelo
A
D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002166:Camptothecin / Q000008:administration & dosage / Q000031:analogs & derivatives; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D000077146:Irinotecan; D019394:Ki-67 Antigen / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D013940:Thymidylate Synthase / Q000378:metabolism*; D016896:Treatment Outcome
D014408:Biomarkers, Tumor; D019394:Ki-67 Antigen; D000077146:Irinotecan; D013940:Thymidylate Synthase; D004264:DNA Topoisomerases, Type I; D005472:Fluorouracil; D002166:Camptothecin