鼻咽癌组织中p16基因的缺失、高甲基化和蛋白的表达及其临床意义

目的探讨鼻咽癌组织中p16基因的缺失、高甲基化和蛋白的表达及其临床意义。方法应用免疫组织化学EnVision法检测90例鼻咽非角化性癌(NKC)组织p16蛋白的表达缺失,聚合酶链反应和甲基化酶切方法检测23例NKC组织p16基因缺失和高甲基化。结果90例NKC中p16蛋白表达阴性率为46.7%(42/90),而对照组的阴性率为0(0/30),P<0.05。p16蛋白表达与NKC患者的5年生存率有明显的相关性,生存期5年内者,其缺失率为60.0%(36/60);生存期5年以上者,其缺失率为20.0%(6/30),P<0.05。有、无远处器官转移的病例p16蛋白阴性率分别为81.8%(9/11)和41.8%(33/79),P<0.05。而有、无颅底破坏和(或)颅神经侵犯病例p16蛋白阴性率分别为41.7%(10/24)和48.5%(32/66),P>0.05。23例NKC中未检测到p16基因外显子1的缺失,但有10例p16基因外显子2的缺失,缺失率为43.4%(10/23);同时检测到2例外显子1的异常甲基化,高甲基化率为8.7%(2/23);总突变率为52.1%(12/23)。结论在NKC的发生发展过程中,p16基因缺失起着重要的作用。p16蛋白表达与NKC患者的5年生存率和远处转移有一定的相关性,而与NKC的局部组织侵犯无明显相关性。

The clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma

Objective To investigate the clinical significance of p16 protein non-expression and p16 gene inactivation by deletions and hypermethylation in nasopharyngeal carcinoma. Methods(Immunohistochemical) study for p16 protein was carried out in 90 cases of non-keratinizing carcinoma (NKC) of nasopharynx. P16 gene deletions and hypermethylation were also analyzed by polymerase chain reaction (PCR) and methylation-specific PCR in 23 randomly selected NKC cases. Results Among the 90 NKC cases studied, 42 cases (46.7%) were negative for p16 protein. The non-expression rate of p16 protein also correlated with the 5-year survival rate. The non-expression rate was 60.0% in patients who died within 5 years, in contrast to 20.0% in those alive for over 5 years after diagnosis. The non-expression rate of p16 protein in cases with or without distant metastasis was 81.8% and 41.8% respectively (P<0.05), while that in cases with or without local invasion into skull base was 41.7% and 48.5% respectively (P>0.05). As for molecular analysis, deletion of p16 gene exon 2 was found in 10 of the 23 cases (43.4%) studied, while deletion of p16 gene exon 1 was not detected in these samples. Hypermethylation of p16 gene exon 1 was also noted in 2 of the 23 cases (8.7%). The overall mutation rate of these cases was 52.1%. Conclusions There is a high incidence of p16 protein non-expression, deletion of p16 gene exon 2 and hypermethylation of p16 gene exon 1 in NKC. P16 gene inactivation may thus play an important role in the pathogenesis of NKC, especially in terms of its metastatic potential.