粒状头样2和表皮生长因子受体蛋白在食管鳞癌中的表达及预后判断价值

Expressions of grainyhead-like 2 and epidermal growth factor receptor in esophageal squamous cell carcinoma and their prognostic significance

目的探讨粒状头样2(grainyhead-like 2,GRHL2)和表皮生长因子受体(epidermal growth factor receptor,EGFR)在食管鳞癌中的表达及对预后判断的意义。方法收集解放军总医院及解放军总医院海南分院根治性切除的食管鳞癌标本63例,应用免疫组化En Vision法检测癌及癌旁正常组织GRHL2和EGFR蛋白的表达。结果 GRHL2和EGFR在食管鳞癌中阳性表达明显高于癌旁正常组织(P均<0.05)。GRHL2高表达与肿瘤大小、分化程度、淋巴结转移、分期显著相关(P均<0.05),EGFR高表达仅与分化程度和分期显著相关(P<0.05)。Spearman相关分析表明GRHL2与EGFR呈负相关(r=-0.359,P=0.004)。Kaplan-Meier生存曲线分析表明GRHL2低表达者的总体生存时间为(32.902±1.017)个月,明显短于高表达者的(54.015±2.208)个月(P=0.000)。GRHL2低表达者的无疾病进展时间为(18.447±1.101)个月,明显短于高表达者的(38.976±1.747)个月(P=0.000)。相反,EGFR高表达者的OS为(36.522±1.931)个月,明显短于低表达者的(48.168±3.331)个月(P<0.05),EGFR高表达者的DFS为(22.190±1.564)个月,明显短于低表达者的(31.810±2.487)个月(P<0.05)。COX回归分析显示GRHL2、淋巴结转移和肿瘤分期是影响食管鳞癌患者术后预后的独立危险因素。结论 GRHL2和EGFR在组织中异常表达可能参与食管鳞癌的发生发展,联合检测GRHL2和EGFR有助于判断食管鳞癌患者的预后。

Objective To investigate the expressions of grainyhead-like2（GRHL2） and epidermal growth factor receptor（EGFR） in esophageal squamous cell carcinoma（ESCC） and their prognostic significance.Methods En Vision immunohistochemical method was used to detect the expressions of GRHL2 and EGFR in ESCC and adjacent normal squamous epithelium in 63 patients who received radical resection of esophageal cancer in Chinese PLA General Hospital and Hainan Branch Hospital.Results GRHL2 and EGFR expressed significantly higher in ESCC than in adjacent normal tissues（P〈0.05,respectively）.The expression of GRHL2 was significantly correlated with tumor size,differentiation,lymph node metastasis and tumor staging（P〈0.05,respectively）.The expression of EGFR was correlated with differentiation degree and tumor staging（P〈0.05,respectively）.Spearman correlation analysis showed a negative correlation between GRHL2 and EGFR（r=-0.359,P=0.004）.Kaplan-Meier survival curve analysis showed that disease free survival（DFS） and overall survival（OS） in patients with GRHL2 low expression were shorter than those with GRHL2 high expression（DFS： 18.447±1.101 vs 38.976±1.7 months; OS： 32.902±1.017 vs 54.015±2.208 months; P= 0.000,respectively）.On the contrary,DFS and OS in patients with EGFR high expression were shorter than those with EGFR low expression（DFS： 22.190±1.564 vs 31.810±2.487 months; OS： 36.522±1.931 vs.48.168±3.331 months; P〈0.05,respectively）.COX regression analysis showed that GRHL2,lymph node metastasis and tumor staging were independent prognostic factors for postoperative ESCC.Conclusion The abnormal expression of GRHL2 and EGFR may be involved in the occurrence and development of ESCC.Combined detection of GRHL2 and EGFR may help to determine the prognosis of patients with ESCC.