Dumontet Charles, Isaac Sylvie, Souquet Pierre-Jean, Bejui-Thivolet Françoise, Pacheco Yves, Peloux Nadine, Frankfurter Anthony, Luduena Richard, Perol Maurice
Inserm U453, Service d'hématologie, Centre hospitalier Lyon-Sud, 69495 Pierre-Bénite Cedex.
Bull Cancer. 2005 Feb;92(2):E25-30.
This study determined the prevalence and the prognostic value of the expression of microtubule components in tumors of 19 patients with non small cell lung cancer receiving taxane-based regimens. Patient samples were stained with antibodies directed against total beta tubulin, classes I, II and III beta tubulin isotypes, delta2 alpha tubulin, tau protein, and the P-gp protein involved in the classical multidrug resistance phenotype. All tumors were stained with pan-beta tubulin antibody and class I tubulin isotype. A majority of the tumor samples expressed class II and class III, although the percentage of positive cells varied significantly between tumors. delta2 alpha tubulin, tau protein and Pgp protein were found in only one tumor sample each. Progression-free survival was shorter (41 days) in patients whose tumors expressed high levels of class III tubulin isotype in comparison to patients with low levels (288 days, p = 0.02). There were 2 responses to chemotherapy among 9 patients (22%) with high levels of class III tubulin vs. 6 among 10 patients (60%) with low levels of expression (Fisher exact test: p = 0.11). These data suggest that high expression of class III tubulin by tumor cells is associated with poor prognosis in patients with NSCLC receiving a taxane-based regimen.
本研究确定了19例接受紫杉烷类方案治疗的非小细胞肺癌患者肿瘤中微管成分表达的患病率及其预后价值。用针对总β微管蛋白、I、II和III类β微管蛋白亚型、δ2α微管蛋白、tau蛋白以及参与经典多药耐药表型的P-糖蛋白的抗体对患者样本进行染色。所有肿瘤均用泛β微管蛋白抗体和I类微管蛋白亚型染色。大多数肿瘤样本表达II类和III类，尽管不同肿瘤之间阳性细胞的百分比差异显著。δ2α微管蛋白、tau蛋白和Pgp蛋白分别仅在一个肿瘤样本中发现。与低水平（288天，p = 0.02）的患者相比，肿瘤表达高水平III类微管蛋白亚型的患者无进展生存期较短（41天）。在9例（22%）III类微管蛋白水平高的患者中有2例对化疗有反应，而在10例（60%）表达水平低的患者中有6例有反应（Fisher精确检验：p = 0.11）。这些数据表明，肿瘤细胞中III类微管蛋白的高表达与接受紫杉烷类方案治疗的非小细胞肺癌患者的不良预后相关。
