肝细胞生长因子受体的定量表达对判定口咽癌预后的价值

Prognostic Value of Quantitating Expression of HGF Receptor Protein for Oropharyngeal Carcinoma

目的:研究肝细胞生长因子受体c-Met在口咽鳞癌中的预后价值。方法:运用一种新的原位蛋白自动定量分析法,研究由108例口咽鳞癌组成的组织微阵列中c-Met抗体染色的形式和蛋白定量表达。结果:c-Met高细胞核染色的肿瘤患者,相对低染色组,其局部复发率明显上升(77%:37%),5年无瘤生存率显著性下降(8%:33%),而且其总体生存率明显下降(8%:35%)。多变量风险回归分析中,c-Met细胞核内的表达状况无论对5年复发率、无瘤生存率和总体生存率都是最有意义的预测因子。但细胞质表达的c-Met与肿瘤的预后不存在关联性。另外,对于c-Met高细胞核表达的肿瘤患者来说,其临床治愈率较低(63%:91%)。细胞质表达的c-Met与MAPK表达密切相关(P<0.001),而细胞核表达的c-Met无此相关性。结论:细胞核内c-Met表达与口咽鳞癌的预后不良相关,这种c-Met的表达方式可能是激发了侵袭性肿瘤的替代传导通路所造成的。

Objective： To determine the prognostic value of quantitating protein expression of the HGF receptor c-Met in patients with oropharyngeal cancer. Methods： A new system of automatic quantitative analysis for protein expression was used to study the levels and pattern of expression of c-Met protein in a tissue microarray composed of 108 oropharyngeal carcinoma cases. Results： Compared to those with light staining, there was an increased local recurrence rate （77% versus 37%）, a decreased 5-year disease-free survival time （8% versus 33%） and a significantly reduced overall survival rate （8% versus 35%） in the samples from patients with high nuclear c-Met levels. In a multivariate Cox regression analysis, intranuelear c-Met expression was the most significant prognostic factor, independent of local recurrenee, disease-free survival time or the overall survival time. However, cytoplasmic c-Met expression was not associated with prognosis. Cytoplasmic c-Met expression was closely correlated with MAPK expression （P〈0.001） but not with nuclear c-Met expression. Conclusion： Intranuelear c-Met expression is related to a poor prognosis for patients with oropharyngeal cancer. Expression of c-Met may be caused by activation of alternative pathways in aggressive tumors.