Ferrandina Gabriella, Zannoni Gian Franco, Martinelli Enrica, Paglia Amelia, Gallotta Valerio, Mozzetti Simona, Scambia Giovanni, Ferlini Cristiano
Department of Oncology, Catholic University, Campobasso, Italy.
Clin Cancer Res. 2006 May 1;12(9):2774-9. doi: 10.1158/1078-0432.CCR-05-2715.
Overexpression of beta III tubulin has been involved in paclitaxel resistance in several experimental models. We investigated the role of beta III tubulin as predictor of clinical outcome in ovarian cancer patients given platinum/paclitaxel treatment. We also investigated whether beta III tubulin expression could be modified after the selective pressure represented by chemotherapy in vivo.
The study was designed to include a series of consecutive ovarian cancer patients with unresectable disease at time of first surgery, who underwent interval debulking surgery with pathologic assessment of response to treatment with platinum/paclitaxel chemotherapy. Immunostaining was done on formalin-fixed, paraffin-embedded tissue sections from pretreatment and posttreatment tissue biopsies by using the polyclonal rabbit anti-class III beta-tubulin antibody.
beta III Tubulin immunoreaction was observed in 51 of 62 (82.2%) cases. beta III Tubulin positivity was neither associated with clinicopathologic variables nor with pathologic response to chemotherapy. Significantly lower percentages of beta III tubulin positivity were observed in posttreatment (range, 5-80%; median, 20%) versus pretreatment (range 10-100%; median, 40%) tissue biopsies (P = 0.0011). Cases with high beta III tubulin expression showed a worse overall survival with respect to cases with low beta III tubulin expression (median overall survival, 25 versus 46 months; P = 0.002). Multivariate analysis showed that high content of beta III tubulin remains independently associated with a worse prognosis.
Assessment of beta III tubulin could be useful to identify poor prognosis ovarian cancer patients candidates to more aggressive and/or targeted therapy.
在多个实验模型中，βIII微管蛋白的过表达与紫杉醇耐药有关。我们研究了βIII微管蛋白作为接受铂类/紫杉醇治疗的卵巢癌患者临床结局预测指标的作用。我们还研究了在体内化疗所代表的选择压力后，βIII微管蛋白表达是否会发生改变。
该研究纳入了一系列初次手术时患有不可切除疾病的连续卵巢癌患者，这些患者接受了间隔减瘤手术，并对铂类/紫杉醇化疗的治疗反应进行了病理评估。使用多克隆兔抗III类β-微管蛋白抗体，对预处理和治疗后组织活检的福尔马林固定、石蜡包埋组织切片进行免疫染色。
62例患者中有51例（82.2%）观察到βIII微管蛋白免疫反应。βIII微管蛋白阳性既与临床病理变量无关，也与化疗的病理反应无关。与预处理组织活检（范围10%-100%；中位数40%）相比，治疗后组织活检中βIII微管蛋白阳性的百分比显著降低（范围5%-80%；中位数20%）（P = 0.0011）。βIII微管蛋白高表达的病例与βIII微管蛋白低表达的病例相比，总生存期更差（总生存期中位数，25个月对46个月；P = 0.002）。多变量分析表明，βIII微管蛋白的高含量仍然独立地与更差的预后相关。
评估βIII微管蛋白可能有助于识别预后不良的卵巢癌患者，这些患者适合更积极和/或靶向治疗。
