食管鳞状细胞癌中p16基因变异的临床意义及地域性差异

Multiple tumor suppressor 1/p16 gene alterations in human esophageal squamous cell carcinoma: clinical significance and regional difference

目的 进一步了解ｐ１６ 基因的变异与食管癌发生发展和生物学行为的关系及地域性差异。方法 采用免疫组化和聚合酶链反应技术，对来自林县高发区和浙江省的食管癌存档组织标本中ｐ１６ 蛋白的表达及基因变异进行了检测，并对食管癌组织中ｐ１６ 基因变异表达的临床意义及地域性差异进行了回顾性比较分析。结果 ９２ 例食管癌组织中，４４ 例存在ｐ１６ 蛋白表达，２２ 例检测到ｐ１６基因的丢失，只有５ 例出现ＰＣＲＳＳＣＰ的异常电泳条带。统计学分析表明，ｐ１６ 蛋白表达与食管癌的病理分期、淋巴结转移及生存期密切相关；而ｐ１６ 基因的丢失与食管癌临床病理指标无关。地域性差异分析表明，Ｔ２ 期病例中，林县的ｐ１６ 蛋白表达显著低于浙江省的同期病例；浙江省食管癌病例ｐ１６ 基因的变异（ 突变＋ 丢失） 与淋巴结转移密切相关，而在林县的食管癌病例中却未见这种相关性。结论ｐ１６ 基因的变异是食管癌发生过程中常见的分子遗传事件，且与食管癌的发展及侵袭转移相关，但突变并非食管癌组织中ｐ１６ 变异的主要形式；河南林县与浙江省食管癌中ｐ１６

Objective To further understand multiple tumor suppressor 1/p16 (mts1/p16) gene alterations in squamous cell esophageal carcinoma (EC) in relation to its biologic behavior and regional difference. Methods Samples of human EC from 92 patients residing in Zhejiang province and in Linxian, Henan province were analyzed for the expression, mutation and deletion of the multiple tumor suppressor gene (mts1/p16) by immunohistochemical staining, polymerase chain reaction and single strand conformation polymorphism. Results mts1/p16 expression at protein level was demonstrated in 44 cases (47.8%). Gene deletion was detected in 22 cases (23.9%) and point mutation in 5 cases (5.4%). Expression of mst1/p16 showed significant correlation with pathologic staging, lymph node status and survival. However, deletion of mst1/p16 did not show correlation with the clinico pathologic parameters. EC patients in stage T 2 from Linxian had significantly lower rate of mst1/p16 protein expression compared to those from Zhejiang province at the same time period. Moreover, there was close association between gene alterations (mutation+deletion) and frequency of lymph node metastasis in Zhejiang EC patients. No such association was observed in EC patients from Linxian. Conclusion msts1/p16 gene alteration is a common genetic event in the carcinogenesis and progression of human esophageal cancer. EC patients from two different regions present differential alterations in mst1/p16 gene.