Gryczyński Maciej, Kobos Józef, Murlewska Anna, Pietruszewska Wioletta
Katedra Otolaryngologii i Klinika Laryngologii UM w Łodzi.
Otolaryngol Pol. 2003;57(3):329-40.
Tumour growth and its progression to a metastatic phenotype involves a serious of genetic events with abnormal activation of oncogenes or inactivation of tumour suppressor genes and others genes connected with proliferation, apoptosis and neovascularisation. The aims of the study were to determine the possible prognostic value of angiogenesis, proliferation index Ki67, p53 and bcl-2 proteins expression in patients with laryngeal cancer. The group of 151 patients with laryngeal cancer, surgically treated with minimum 5 years observation, was multi-variously analysed. Paraffin--embedded tissue sections from each case were stained with a monoclonal antibody raised against FVIII antigen, p53 and bcl-2 proteins and Ki67 proliferation antigen using a peroxidase labelled streptavidin--biotin kit in standard immunohistochemistry techniques. In univariate analysis: staging IV, tumour size T4, nodal metastasis N2 and N3, local and nodal recurrences, high expression of Ki67 and P53, high (over median) IA measured as number of microvessels with FVIII expression were significantly associated with shortened overall survival. Disease-free survival was related to: proliferation index Ki67, expression of P53 protein and angiogenesis measured as microvessels density with expression of FVIII antigen. In multivariate analysis the most important death risk factors for overall survival were: tumour size, nodal metastasis, local and nodal recurrences, P53 protein expression and IA measured as number of microvessels with FVIII expression. In multivariate analysis of disease-free survival only P53 protein expression, proliferative index Ki67 and expression of FVIII had independent prognostic value. Intensity of angiogenesis, proliferation index of Ki67 antigen and expression of P53 protein were independent predictors of patients with laryngeal cancer outcome. In contrary Bcl2 protein seems to be useless in these patients.
肿瘤生长及其向转移表型的进展涉及一系列基因事件，包括癌基因的异常激活或肿瘤抑制基因以及其他与增殖、凋亡和新血管形成相关基因的失活。本研究的目的是确定血管生成、增殖指数Ki67、p53和bcl-2蛋白表达在喉癌患者中的可能预后价值。对151例接受手术治疗且至少观察5年的喉癌患者进行了多方面分析。使用过氧化物酶标记的链霉亲和素-生物素试剂盒，采用标准免疫组织化学技术，用针对FVIII抗原、p53和bcl-2蛋白以及Ki67增殖抗原的单克隆抗体对每个病例的石蜡包埋组织切片进行染色。单因素分析显示：IV期、肿瘤大小T4、淋巴结转移N2和N3、局部和淋巴结复发、Ki67和P53的高表达、以FVIII表达的微血管数量测量的高（超过中位数）IA与总生存期缩短显著相关。无病生存期与以下因素有关：增殖指数Ki67、P53蛋白表达以及以FVIII抗原表达的微血管密度测量的血管生成。多因素分析显示，总生存期最重要的死亡风险因素为：肿瘤大小、淋巴结转移、局部和淋巴结复发、P53蛋白表达以及以FVIII表达的微血管数量测量的IA。在无病生存期的多因素分析中，只有P53蛋白表达、增殖指数Ki67和FVIII表达具有独立的预后价值。血管生成强度、Ki67抗原增殖指数和P53蛋白表达是喉癌患者预后的独立预测因素。相反，Bcl2蛋白在这些患者中似乎没有作用。
