Stathmin and Tubulin Expression and Survival of Ovarian Cancer Patients Receiving Platinum Treatment With and Without Paclitaxel

BACKGROUND: Paclitaxel interacts with microtubules to exert therapeutic effects. Molecules that affect microtubule activity, such as beta III-tubulin and stathmin, may interfere with the treatment. In this study, the authors analyzed beta III-tubulin and stathmin expression in ovarian tumors and examined their associations with treatment response and patient survival. METHODS: The study included 178 patients with epithelial ovarian cancer who underwent cytoreductive surgery followed by platinum-based chemotherapy; of these patients, 75 also received paclitaxel. Fresh tumor samples that were collected at surgery were analyzed for messenger RNA expression of beta III-tubulin and stathmin using real-time polymerase chain reaction analysis. Associations of these molecules with treatment response, disease progression, and overall survival were evaluated. RESULTS: High stathmin expression was associated with worse disease progression-free and overall survival compared with low stathmin expression. This association was independent of patient age, disease stage, tumor grade, histology, and residual tumor size and was observed in patients who received platinum plus paclitaxel, but not in patients who received platinum without paclitaxel, suggesting that stathmin expression in tumor tissue may interfere with paclitaxel treatment. Similar effects were not observed for beta III-tubulin, although high beta III-tubulin expression was associated with disease progression among patients who received platinum without paclitaxel. No associations were observed between treatment response and tubulin or stathmin expression. Expression levels of beta III-tubulin and stathmin were correlated significantly. CONCLUSIONS: High stathmin expression predicted an unfavorable prognosis in patients with ovarian cancer who received paclitaxel and platinum chemotherapy. This finding supports the possibility that stathmin may interfere with paclitaxel treatment, leading to a poor prognosis for patients with ovarian cancer. Cancer 2009;115:2453-63. (C) 2009 American Cancer Society.