Sève Pascal, Reiman Tony, Lai Raymond, Hanson John, Santos Cheryl, Johnson Lorelei, Dabbagh Laith, Sawyer Michael, Dumontet Charles, Mackey John R
Department of Internal Medicine, Hôtel Dieu, 1 Place de l'Hôpital, Hospices Civils de Lyon, 69288, Lyon Cedex 02, France.
Cancer Chemother Pharmacol. 2007 Jun;60(1):27-34. doi: 10.1007/s00280-006-0343-1. Epub 2006 Sep 22.
In this study, we determine the prevalence and the prognostic value of the class III beta-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 beta-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 beta-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 beta-tubulin isotype had shorter overall survival, while there was a trend for an association with progression free survival. Multivariate analysis showed that class III beta-tubulin expression was independently correlated with progression free survival and overall survival.
These findings suggest that a high level of expression of class III beta-tubulin in tumor cells is associated with resistance to paclitaxel and decreased survival in patients with carcinomas of unknown primary receiving paclitaxel-based chemotherapy.
在本研究中，我们测定了经基于紫杉醇的化疗治疗的40例原发部位不明的癌患者肿瘤中，通过免疫组织化学检测的III类β-微管蛋白微管蛋白的患病率及其预后价值。
对免疫组织化学染色强度和细胞百分比进行定量。评估临床特征、对化疗的反应、无进展生存期和总生存期与III类β-微管蛋白表达的关系。
缓解率为17.9%（39例有价值的患者中有7例部分缓解），11例患者病情稳定（28.2%），21例患者在治疗中病情进展（53.8%）。III类β-微管蛋白高表达的患者对紫杉烷类化疗更耐药，定义为治疗期间病情进展，而未发现患者特征与化疗反应相关。肿瘤表达高水平III类β-微管蛋白亚型的患者总生存期较短，而与无进展生存期存在关联趋势。多变量分析表明，III类β-微管蛋白表达与无进展生存期和总生存期独立相关。
这些发现表明，肿瘤细胞中高水平的III类β-微管蛋白表达与接受基于紫杉醇的化疗的原发部位不明的癌患者对紫杉醇的耐药性及生存期缩短有关。
