βV-tubulin expression is associated with outcome following taxane-based chemotherapy in non-small cell lung cancer

BACKGROUND: Tubulin-binding agents (TBAs) are effective in non-small cell lung cancer (NSCLC) treatment. Both beta III- and beta V-tubulins are expressed by cancer cells and may lead to resistance against TBAs. METHODS: Pre-treatment samples from 65 locally advanced or oligometastatic NSCLC patients, who underwent uniform induction chemotherapy with paclitaxel and platinum followed by radiochemotherapy with vinorelbine and platinum were retrospectively analysed by immunohistochemistry. Protein expression of beta III- and beta V-tubulin was morphometrically quantified. RESULTS: Median pre-treatment H-score for beta III-tubulin was 110 (range: 0-290), and 160 for beta V-tubulin (range: 0-290). Low beta III-tubulin expression was associated with improved overall survival (OS) (P = 0.0127, hazard ratio (HR): 0.328). An association between high beta V-tubulin expression and prolonged progression-free survival (PFS, median 19.2 vs 9.4 months in high vs low expressors; P = 0.0315, HR: 1.899) was found. Further, high beta V-tubulin expression was associated with objective response (median H-score 172.5 for CR + PR vs 120 for SD + PD patients, P = 0.0104) or disease control following induction chemotherapy (170 for CR + PR + SD vs 100 for PD patients, P = 0.0081), but not radiochemotherapy. CONCLUSION: Expression of beta V-tubulin was associated with treatment response and PFS following paclitaxel-based chemotherapy of locally advanced and oligometastatic NSCLC patients. Prolonged OS was associated with low levels of beta III-tubulin. Prospective evaluation of beta III/beta V-tubulin expression in NSCLC is warranted. British Journal of Cancer (2012) 107, 823-830. doi:10.1038/bjc.2012.324 www.bjcancer.com Published online 26 July 2012 (C) 2012 Cancer Research UK