应用组织微阵列技术分析各期鼻咽癌组织p16的表达

目的　构建高通量组织微阵列 /组织芯片 (high throughputtissuemicroarray/tissuechip) ,明确p16基因表达与鼻咽癌的相关性及探讨组织芯片技术的可行性。方法　用组织阵列仪制备按不同临床分期排布的组织芯片 ,然后用免疫组织化学LSAB法检测一张组织芯片上 2 5 9例鼻咽活检组织样本中p16蛋白表达 ,并分析p16蛋白表达在鼻咽癌组织的分布状况及其与临床分期的相关性。结果在正常鼻咽黏膜组织、Ⅰ～Ⅳ期及未分期鼻咽癌组织中p16蛋白的缺失情况分别为 0 / 18、3/ 3、86 3%(38/ 44 )、86 8% (5 9/ 6 8)、82 1% (2 3/ 2 8)、88 8% (87/ 98)。鼻咽癌组织中p16蛋白表达率低于鼻咽非癌组织 (χ2 =82 5 8,P <0 0 0 1) ,p16蛋白表达与鼻咽癌的临床分期无显著相关性 (χ2 =0 0 9,P =0 76 9)。结论　鼻咽癌中p16蛋白的高频缺失提示p16基因在鼻咽癌的发生发展中起重要作用 ,而这种表达缺失在早晚期鼻咽癌中的一致性又提示p16蛋白缺失是鼻咽癌形成过程中的一个早期事件。应用组织芯片大规模高效检测临床组织样本是可行的 ,具有快速、方便、经济、准确的特点。

Rapid tissue microarray assay of p16 protein expression for different stage nasopharyngeal carcinoma

OBJECTIVE: To effectively screen p16 protein expression of different clinical stage nasopharyngeal carcinoma (NPC) by constructing and applying high-throughput tissue microarray/tissue chip. METHODS: A series of tissue chips were prepared by using tissue arrayer with samples from different clinical stage NPC tumors and noncancerous nasopharynx tissue. Specimens from 259 cases of nasopharyngeal lesions were detected immunohistochemically on a tissue chip for p16 protein expression and the correlation of p16 protein expression to clinical stage of NPC was analyzed statistically. RESULTS: p16 protein expression was detected in all 18 histologically normal nasopharyngeal epithelia. No p16 protein was detected in 3 of 3 (100%) stage I NPC, 38 of 44 (86.3%) stage II NPC, 59 of 68 (86.8%) stage III NPC, 23 of 28 (82.1%) stage IV NPC, 87 of 98 (88.8%) unclear stage NPC. The efficiency of p16 protein expression in NPC tissues was significantly lower than that in normal nasopharyngeal epithelia (chi(2) = 82.58, P < 0.001), and there was no apparent relationship between p16 protein expression and clinical stages (chi(2) = 0.09, P = 0.769). CONCLUSIONS: The frequent deletion of p16 protein in NPC suggests that p16 gene has an important role in the development and progression of NPC. The consistency of p16 protein deletion in different stages of NPC suggests that the deletion of p16 protein is an early event in the development of NPC, and it is feasible to utilize tissue microarray for a rapid, economic and accurate screening of clinical tissue specimens on a large scale.