乏氧诱导因子1α在食管鳞癌中的表达及其与化疗疗效的关系

目的 观察乏氧诱导因子（HIF）1α在食管鳞癌组织中的表达及其与化疗疗效及临床预后的关系。方法48例中晚期食管鳞癌患者以顺铂／紫杉醇为基础的联合方案化疗,紫杉醇175mg／m^2,第1天,静脉滴注3h;顺铂80mg／m^2,分别在第2-4天,21 d为1个周期。每例至少完成2个周期的化疗,疗效评价明确。上述病例标本来自郑州大学第一附属医院病理科。免疫组织化学检测HIF-1α在食管癌组织中的表达,另取20例正常食管黏膜作对照。应用χ^2检验、Kaplan-Merier法进行统计学分析。结果食管鳞癌组织中HIF-1α阳性染色主要位于癌细胞胞质／核内,阳性率43．75％（21／48）,而正常食管黏膜均呈阴性表达。HIF-1α阳性表达者化疗有效率23．81％（5／21）显著低于HIF-1α阴性表达者的化疗有效率70．37％（19／27）（P〈0．05）。HIF-1α阳性表达者中位疾病进展时间为2．0个月,中位生存时间为6．0个月,2年生存率为13．3％;而HIF-1α阴性表达者中位疾病进展时间为5．0个月,中位生存时间为11．0个月,2年生存率为42．2％。两组间比较差异有统计学意义（P〈0．05）。结论免疫组织化学法检测HIF-1α蛋白表达可作为临床上预测食管癌化疗疗效及临床预后的的指标之一。

Relationship between the expression of hypoxia-inducible factor-1alpha and chemotherapy response in esophageal squamous cell carcinoma

OBJECTIVE: To observe the relationship between expression of hypoxia-inducible factor (HIF)-1alpha and chemotherapy response and clinical outcome. METHODS: Platixal in combination with cisplatin was used in 48 patients with ESCC at advanced stage. platixal 175 mg/m(2), d1; cisplatin 80 mg/m(2), d 2, d 3, d 4, 21 days was one cycle. Chemotherapy response was evaluated. Specimens mentioned above comes from pathology department, the first affiliated hospital of Zhengzhou university. Immuno-histochemistry was used to examine the expression of HIF-1alpha protein in esophageal squamous cell carcinoma. 20 cases normal tissue of esophaguo was used as control group. chi(2) test and Kaplan-Merier was used to analysis data. RESULTS: HIF-1alpha immunoreactivity was recognized in both cytoplasm and nuclei. HIF-1alpha protein positive expression rate was 43.75% (21/48) in tumor samples, and was negative expression in normal tissue. Among 21 cases with positive expression of HIF-1alpha, there was none complete response case and 5 cases of partial responses, and the response rate was 23.81%; whereas in 27 cases with negative expression of HIF-1alpha, there were 8 cases of complete response and 11 cases of partial responses, and the response rate was 70.37%. There was significant difference between two groups (P < 0.05). In patients of HIF-1alpha positive expression, the median time to tumor progression was 2.0 months, and the median actuarial survival was 6 months, and survival rate was 13.3% in two years; Whereas in patients of HIF-1alpha negative expression, the median time to tumor progression was 5.0 months, and the median actuarial survival was 11.0 months, and survival rate was 42.2% in two years. There was significant difference between two groups (P < 0.05). CONCLUSION: HIF-1alpha protein expression by immunohistochemistry may be a useful indicator to prediction the chemotherapy response and clinical outcome for esophageal squamous cell carcinoma.