Popov Zivko, Gil-Diez-De-Medina Sixtina, Ravery Vincent, Hoznek Andras, Bastuji-Garin Sylvie, Lefrere-Belda Marie-Aude, Abbou Claude C, Chopin Dominique K
Centre de Recherches Chirurgicales Henri Mondor, Faculté de Médicine, Université Paris-12 Val de Marne, INSERM EMI 03-37, 94010 Creteil, France.
Urol Oncol. 2004 Mar-Apr;22(2):93-101. doi: 10.1016/j.urolonc.2004.01.001.
Changes in growth factor receptor expression may confer a growth advantage on tumour cells. Epidermal growth factor-receptor (EGF-R) has been associated with the genesis of bladder tumours. We sought a link between EGF-R expression and MIB-1 cell proliferation and examined their prognostic value in the progression of bladder cancer. Fresh frozen samples from 113 transitional cell carcinomas (TCC) of the bladder and 10 healthy bladders were studied by immunohistochemistry, using monoclonal antibodies for EGF-R expression and MIB-1 for cell proliferation. Qualitative and quantitative immunostaining were analyzed in relation to time to progression and compared with clinical and pathologic parameters for prognostic significance in univariate and multivariate analysis (stepwise logistic regression). EGF-R stained more intensively in invasive tumours. Median nuclear over-expression of MIB-1 was 28%. Progression free survival rate estimates (log rank test) were significantly lower in patients EGF-R positive and with MIB-1 score above 28% (P < 0.0001, P < 0.0001, respectively). Multivariate analysis indicated that MIB-1 immunostaining was the most significant independent variable and EGF-R expression had no additional prognostic value over clinical stage and grade and cell proliferation. The MIB-1 proliferation index is a stronger predictor of bladder tumour progression than is EGF-R over-expression. This marker yield significant prognostic information in addition to stage and grade and may be of value for the clinical management of superficial and invasive bladder carcinomas. The pattern of EGF-R immunostaining and its association with tumour progression makes it a candidate for antigrowth factor therapy.
生长因子受体表达的改变可能赋予肿瘤细胞生长优势。表皮生长因子受体（EGF-R）已被证实与膀胱肿瘤的发生密切相关。我们旨在探寻EGF-R表达与MIB-1细胞增殖之间的联系，并研究它们在膀胱癌进展中的预后价值。采用免疫组织化学方法，使用针对EGF-R表达的单克隆抗体和针对细胞增殖的MIB-1，对113例膀胱移行细胞癌（TCC）新鲜冷冻样本及10例健康膀胱组织进行研究。针对进展时间分析定性和定量免疫染色，并与临床和病理参数进行比较，以在单因素和多因素分析（逐步逻辑回归）中评估预后意义。EGF-R在浸润性肿瘤中染色更为强烈。MIB-1的核过表达中位数为28%。EGF-R阳性且MIB-1评分高于28%的患者无进展生存率估计值（对数秩检验）显著更低（分别为P < 0.0001，P < 0.0001）。多因素分析表明，MIB-1免疫染色是最显著的独立变量，而EGF-R表达在临床分期、分级和细胞增殖之外并无额外的预后价值。MIB-1增殖指数比EGF-R过表达更能有力地预测膀胱肿瘤进展。除分期和分级外，该标志物还能提供重要的预后信息，可能对浅表性和浸润性膀胱癌的临床管理具有价值。EGF-R免疫染色模式及其与肿瘤进展的关联使其成为抗生长因子治疗的候选对象。
