Class III β-tubulin is a marker of paclitaxel resistance in carcinomas of unknown primary site
In this study, we determine the prevalence and the prognostic value of the class III β-tubulin microtubule protein examined immunohistochemically, in tumors of 40 patients with carcinomas of unknown primary site treated with paclitaxel-based chemotherapy. Immunohistochemical intensity of staining and percentage of cells were quantified. Clinical characteristics, response to chemotherapy, progression-free survival, and overall survival were assessed for relationships with the expression of class III β-tubulin. The response rate was 17.9% (seven partial responses among 39 valuable patients), while eleven patients had a stable disease (28.2%) and 21 patients progressed on therapy (53.8%). Patients with high class III β-tubulin expression were more resistant to taxane-based chemotherapy, defined as progression under treatment, while patient characteristics were not found to be correlated with response to chemotherapy. Patients whose tumors expressed high levels of class III β-tubulin isotype had shorter overall survival, while there was a trend for an association with progression free survival. Multivariate analysis showed that class III β-tubulin expression was independently correlated with progression free survival and overall survival. These findings suggest that a high level of expression of class III β-tubulin in tumor cells is associated with resistance to paclitaxel and decreased survival in patients with carcinomas of unknown primary receiving paclitaxel-based chemotherapy.