High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer.
High levels of class III β-tubulin expression are associated with aggressive tumor features in breast cancer.
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DOI：
10.3892/ol.2016.4206
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发表时间：
2016-03
期刊：
影响因子：
2.9
通讯作者：
Quaas A
中科院分区：
文献类型：
--
作者：
Lebok P;Öztürk M;Heilenkötter U;Jaenicke F;Müller V;Paluchowski P;Geist S;Wilke C;Burandt E;Lebeau A;Wilczak W;Krech T;Simon R;Sauter G;Quaas A
III类β-微管蛋白（TUBB 3）的过表达是一种赋予微管动态特性的因子，是乳腺癌和其他类型实体癌对微管靶向化疗药物耐药性的候选生物标志物。关于TUBB 3表达水平与乳腺癌表型和患者预后的相关性，与先前研究的结果不一致，促使本研究在具有可用临床随访数据的大型乳腺癌病例队列中研究TUBB 3表达。通过免疫组织化学分析预先存在的乳腺癌预后组织微阵列（包含来自2，197名乳腺癌个体患者的单个0.6 mm组织核心）的TUBB 3表达。本研究的结果显示，TUBB 3在小叶乳腺癌病例中的表达频率较低（34%），与其他组织学类型的癌症病例相比，包括非特殊类型的乳腺癌（60%; P<0.0001）。高TUBB 3阳性与高肿瘤分级（P<0.0001）、雌激素（P<0.0001）和孕激素受体（P<0.004）阴性、人表皮生长因子2扩增（P<0.0001）和三阴性表型（P<0.0001）相关。如果联合分析任何组织学的所有乳腺癌病例，TUBB 3过表达还与患者生存率降低相关（P=0.0088）;然而，这种联系在非特殊类型的乳腺癌病例亚组中或在包括肿瘤分期、分级和淋巴结分期的既定预后因素的多变量分析中并不明显。总之，本研究表明，TUBB 3过表达与乳腺癌的不良特征相关，与其他组织学亚型相比，TUBB 3在小叶乳腺癌病例中可能具有独特的作用。本研究的结果不支持TUBB 3作为乳腺癌预后标志物的临床相关作用。
Overexpression of class III β-tubulin (TUBB3), a factor that confers dynamic properties to microtubules, is a candidate biomarker for resistance to microtubule-targeting chemotherapeutics in breast and other types of solid cancer. Discrepant results from previous studies, with respect to the association of TUBB3 expression levels with breast cancer phenotype and patient prognosis, prompted the present study to investigate TUBB3 expression in a large cohort of breast cancer cases, with available clinical follow-up data. A preexisting breast cancer prognosis tissue microarray, containing a single 0.6 mm tissue core from each of 2,197 individual patients with breast cancer, was analyzed for TUBB3 expression by immunohistochemistry. The results of the present study revealed that TUBB3 expression was less frequent in lobular breast cancer cases (34%), compared with that of cancer cases of alternative histologies, including breast cancer of no special type (60%; P<0.0001). High TUBB3 positivity was associated with high tumor grade (P<0.0001), negativity for estrogen (P<0.0001) and progesterone receptors (P<0.004), as well as the presence of human epidermal growth factor 2 amplification (P<0.0001) and a triple-negative phenotype (P<0.0001). TUBB3 overexpression was additionally associated with reduced patient survival if all breast cancer cases of any histology were jointly analyzed (P=0.0088); however this link was not evident in the subset of breast cancer cases of no special type, or in a multivariate analysis including the established prognostic factors of tumor stage, grade and nodal stage. In conclusion, the present study demonstrated that TUBB3 overexpression was associated with adverse features of breast cancer, and that TUBB3 may possess a distinct role in lobular breast cancer cases, compared with alternative histological subtypes. The results of the present study do not support a clinically relevant role for TUBB3 as a prognostic marker in breast cancer.
影响因子：
3.7
作者：
Jung M;Koo JS;Moon YW;Park BW;Kim SI;Park S;Lee SH;Hong S;Rha SY;Chung HC;Kim JH;Sohn J
通讯作者：
Sohn J