Expression of beta-tubulin isotypes in human primary ovarian carcinoma
Expression of beta-tubulin isotypes in human primary ovarian carcinoma
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DOI：
10.1016/j.ygyno.2007.01.044
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发表时间：
2007-06-01
影响因子：
4.7
通讯作者：
Tsuneyoshi, Masazumi
中科院分区：
文献类型：
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作者：
Ohishi, Yoshihiro;Oda, Yoshinao;Tsuneyoshi, Masazumi
Objective.β-微管蛋白同种型的选择性表达已被报道是紫杉烷耐药的重要机制之一。本研究的目的是评估β-微管蛋白同种型的免疫组织化学表达，使用紫杉烷类治疗的卵巢癌的临床样本，并检查是否每种β-微管蛋白同种型的蛋白质水平与临床特征相关。我们检测了77例卵巢癌患者（54例接受紫杉烷为基础的方案治疗，23例接受无紫杉烷方案治疗）的肿瘤样本，使用免疫组化检测β-微管蛋白同种型（I类，II类，III类和IV类）表达的内在蛋白水平，并评估了该蛋白水平与临床特征的相关性。根据免疫反应阳性肿瘤细胞的比例和强度对表达水平进行评分。在总共77例卵巢癌中证实了I类和IV类β-微管蛋白的高蛋白水平，II类β-微管蛋白的极低蛋白水平，以及III类β-微管蛋白表达的中间蛋白水平。至于从54名接受紫杉烷治疗的患者中采集的样本，40个样本显示出不可检测的II类β-微管蛋白水平。II类β-微管蛋白表达缺失组与晚期（p=0.024）和短期无进展生存期（对数秩检验，p=0.022）显著相关。多变量分析表明，短期无进展生存期的唯一显著独立预后指标是晚期，尽管III类β-微管蛋白的高表达也倾向于与短期无进展生存期相关，但不显著（p=0.081）。在23例接受无紫杉烷方案治疗的患者中，未发现此类相关性或倾向。在紫杉烷类药物治疗的卵巢癌病例中，III类β-微管蛋白的高表达似乎与早期复发有关，这被认为可能是耐药复发。此外，II类β-微管蛋白表达的丧失与晚期相关，这可能代表侵袭性肿瘤进展。(c)2007年爱思唯尔公司All rights reserved.
Objective. Selective expression of beta-tubulin isotypes has been reported to be one of the important mechanisms of taxane resistance. The purpose of this study was to evaluate the immunohistochemical expression of beta-tubulin isotypes using clinical samples of ovarian carcinoma treated by taxanes and to examine whether the protein levels of each of the beta-tubulin isotypes were correlated with the clinical features.Experimental design. We examined tumor samples taken from 77 ovarian carcinoma patients (54 patients treated with a taxane-based regimen and 23 treated with a taxane-free regimen), for the intrinsic protein level of beta-tubulin isotype (classes I, II, III and IV) expression using immunohistochemistry, and we evaluated the correlation of this protein level with the clinical features. The expression levels were scored by the proportion and intensity of the immunoreactive tumor cells.Results. High protein levels of classes I and IV beta-tubulin, and very low protein levels of class II beta-tubulin, and intermediate protein levels of class III beta-tubulin expression were demonstrated in a total of 77 ovarian carcinomas. As for the samples taken from the 54 patients treated with the taxane-based regimen, 40 samples demonstrated undetectable levels of class II beta-tubulin protein. The class II beta-tubulin expression-absent group was significantly correlated with advanced stage (p=0.024) and with a short period of progression-free survival (log-rank test, p=0.022). Multivariate analyses demonstrated that the only significant independent prognostic indicator of a short period of progression-free survival was advanced stage, although a high expression of class III beta-tubulin was also prone to be associated with a short period of progression-free survival, but not significantly so (p=0.081). No such correlations or propensities were demonstrated in the 23 patients treated with the taxane-free regimen.Conclusions. In cases of ovarian carcinoma treated by taxanes, high expression of class III beta-tubulin seems to be associated with earlier recurrence, which is believed likely to be resistant relapse. In addition, loss of class II beta-tubulin expression is correlated with advanced stage, which may represent aggressive tumor progression. (c) 2007 Elsevier Inc. All rights reserved.