Expression of Class III β-Tubulin Is Predictive of Patient Outcome in Patients with Non–Small Cell Lung Cancer Receiving Vinorelbine-Based Chemotherapy

• Published in: Clinical cancer research 2005-08, Vol.11 (15), p.5481-5486
• Main Authors: SEVE, Pascal, ISAAC, Sylvie, TREDAN, Olivier, SOUQUET, Pierre-Jean, PACHECO, Yves, PEROL, Maurice, LAFANECHERE, Laurence, PENET, Aurélie, PEILLER, Eva-Laure, DUMONTET, Charles
• Format: Article
• Language: English
• Subjects: Antineoplastic agents; Biological and medical sciences; Chemoresistance; Medical sciences; Non–small cell lung cancer; Pharmacology. Drug treatments; Pneumology; Tubulin; Tubulin III; Tumors of the respiratory system and mediastinum; Vinorelbine
• ISSN: 1078-0432; 1557-3265
• DOI: 10.1158/1078-0432.CCR-05-0285

Purpose: To determine the prevalence and the prognostic value of microtubule component expression in tumors of patients with locally advanced or metastatic non–small cell lung cancer (NSCLC). Experimental Design: Expression of microtubular components was immunohistochemically examined in 93 tumor samples from untreated patients with stage III and IV NSCLC. All patients received vinorelbine-based chemotherapy. Response to chemotherapy, progression-free survival, and overall survival were correlated with the expression of microtubule proteins. Results: The response rate was 27.3% (21 partial responses among 77 valuable patients). Although expression of microtubule components was not associated with the response rate, high class III β-tubulin expression was correlated with resistance to vinorelbine, defined as disease progression under treatment. Patients whose tumors expressed high levels of class III β-tubulin isotype had shorter progression-free survival and overall survival ( P = 0.002 and 0.001, respectively). High Δ2 α-tubulin expression was associated with a shorter overall survival ( P = 0.018). Tubulin II levels were not found to be correlated with patient outcome. A multivariate analysis, taking into account sex, age, histology, stage, weight loss, and class II β-tubulin, class III β-tubulin, and Δ2 α-tubulin levels, confirmed that class III β-tubulin expression was independently correlated with progression-free survival ( P = 0.04) and overall survival ( P = 0.012). Conclusions: These findings suggest that a high level of expression of class III β-tubulin in tumor cells is associated with resistance to vinorelbine and a poor prognosis in patients with NSCLC receiving vinorelbine-based chemotherapy.