Protein abundance of class III beta-tubulin but not Delta2-alpha-tubulin or tau is related to paclitaxel response in carcinomas of unknown primary site.
OBJECTIVE
To determine the prognostic value of microtubule component expression in tumors of patients with carcinomas of unknown primary site (CUP).


METHODS
Class III beta-tubulin, Delta2-alpha-tubulin and tau protein were examined immunohistochemically in 51 CUP tumors from patients receiving paclitaxel and compared with their response to treatment.


RESULTS
The overall response rate was 18.4% among 49 evaluable patients. Delta2-alpha-Tubulin and tau were not correlated with response or patient outcome. High class III beta-tubulin expression was correlated with both resistance to chemotherapy and shorter overall survival, while there was no relation with progression-free survival. In multivariate analysis taking into account clinical factors, class III beta-tubulin expression was independently correlated with overall survival.


CONCLUSIONS
These findings show that in tumor cells a high level of expression of class III beta-tubulin, but not Delta2-alpha-tubulin or tau, is associated with resistance to paclitaxel and a poor prognosis in CUP patients receiving paclitaxel.
Sève
Pascal
P
Université Claude Bernard Lyon 1, INSERM U 590, Lyon, France. pascal.seve@chu-lyon.fr
Reiman
Tony
T
Isaac
Sylvie
S
Trillet-Lenoir
Véronique
V
Lafanéchère
Laurence
L
Sawyer
Michael
M
Dumontet
Charles
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D016190:Carboplatin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008870:Microtubules / Q000187:drug effects / Q000378:metabolism; D008875:Middle Aged; D015999:Multivariate Analysis; D009362:Neoplasm Metastasis; D009382:Neoplasms, Unknown Primary / Q000188:drug therapy* / Q000378:metabolism*; D017239:Paclitaxel / Q000008:administration & dosage; D020033:Protein Isoforms; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism*; D016875:tau Proteins / Q000378:metabolism*
C054369:MAPT protein, human; D020033:Protein Isoforms; D014404:Tubulin; D016875:tau Proteins; D016190:Carboplatin; D017239:Paclitaxel