title: Class III beta-tubulin expression in tumor cells predicts response and outcome in patients with non-small cell lung cancer receiving paclitaxel.
abstract: Both fundamental and clinical studies suggest that class III beta-tubulin expression is associated with resistance to taxanes and constitutes a prognostic factor in several solid tumors. In this study, we assessed the prognostic and predictive value of class III beta-tubulin in tumors of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) treated with paclitaxel-based or other regimens that did not include tubulin-binding agents. Expression of class III beta-tubulin was examined immunohistochemically in 91 tumor samples obtained before treatment from patients with stage III and IV NSCLC, including 47 who received paclitaxel-based regimens and 44 who received regimens without tubulin-binding agents. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of class III beta-tubulin protein. The response rate was 37.5% (16 responses among 45 evaluable patients) among patients receiving paclitaxel. Patients whose tumors expressed low levels of class III beta-tubulin isotype had a better response rate, longer progression-free survival, and overall survival (P < 0.001, 0.004, and 0.002, respectively), whereas this variable was not found to be predictive in patients receiving regimens without tubulin-binding agents. A multivariate analysis taking into account sex, age, histology, stage, and class III beta-tubulin confirmed that low-level class III beta-tubulin expression was independently correlated with progression-free survival (P = 0.003) and overall survival (P = 0.003). These findings suggest that the expression levels of class III beta-tubulin in tumor cells is predictive of response to therapy and patient outcome in patients with NSCLC receiving paclitaxel-based chemotherapy but is not a general prognostic factor in this patient population.
authors.affiliation: Service de Médecine Interne, Hospices Civils de Lyon, France.
authors.forename: Pascal
authors.initials: P
authors.lastname: Sève
authors.forename: John
authors.initials: J
authors.lastname: Mackey
authors.forename: Sylvie
authors.initials: S
authors.lastname: Isaac
authors.forename: Olivier
authors.initials: O
authors.lastname: Trédan
authors.forename: Pierre-Jean
authors.initials: PJ
authors.lastname: Souquet
authors.forename: Maurice
authors.initials: M
authors.lastname: Pérol
authors.forename: Raymond
authors.initials: R
authors.lastname: Lai
authors.forename: Alain
authors.initials: A
authors.lastname: Voloch
authors.forename: Charles
authors.initials: C
authors.lastname: Dumontet
mesh_terms: D000328:Adult; D000368:Aged; D000972:Antineoplastic Agents, Phytogenic / Q000627:therapeutic use*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D018572:Disease-Free Survival; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D017239:Paclitaxel / Q000627:therapeutic use*; D016019:Survival Analysis; D016896:Treatment Outcome; D014404:Tubulin / Q000378:metabolism*
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D014404:Tubulin; D017239:Paclitaxel