非Hodgkin淋巴瘤p16基因和蛋白的表达

Expression of p16 gene in malignant lymphoma detected by immunohistochemical and in situ hybridization techiques

目的探讨在非Ｈｏｄｇｋｉｎ淋巴瘤（ＮＨＬ）中ｐ１６基因的表达情况及临床病理意义。方法应用免疫组化ＬＳＡＢ法和原位杂交技术检测６４例ＮＨＬｐ１６蛋白及ｐ１６ｍＲＮＡ表达情况，同时结合病人的临床病理资料进行分析。结果６４例ＮＨＬ中，ｐ１６蛋白阳性表达率５３１％，阴性率４６９％，阳性反应以胞核分布为主。６４例ＮＨＬｐ１６ｍＲＮＡ阳性表达率７０３％，阴性率２９７％，阳性信号显示于胞浆中。ｐ１６蛋白及ｐ１６ｍＲＮＡ在ＮＨＬ中的阳性表达与患者性别，年龄及免疫分型无明显相关性，但均与组织分化程度明显相关，高度恶性组的阳性率分别为３３３％及４６７％，低度恶性组的阳性率分别为７１４％及８５７％（Ｐ＜００５），随访发现均与预后相关。结论ＮＨＬ存在较高比例的ｐ１６ｍＲＮＡ及ｐ１６蛋白阴性表达，说明在ＮＨＬ的发生发展中，ｐ１６基因失活起着重要作用。ＮＨＬ中ｐ１６ｍＲＮＡ比ｐ１６蛋白阴性表达率低，提示与转录后调节、ｍＲＮＡ或蛋白不稳定有关。两者的阳性表达均有一定的预后意义。

Objective To investigate the expression of p16 gene in non Hodgkin′s lymphoma (NHL) and its clinicopathological significance. Methods Paraffin embedded biopsies from 64 patients with NHL were analysed for p16 gene expression by immunohistochemical methods and in situ hybridization technique. Results Of the 64 NHL cases, 34(53.1%) were positive for p16 protein, 30(46.9%) lacked p16 protein, most of the positive signals were seen in the nuclei; 45(70.3%) were p16 mRNA positive, 19(29.7%) lost p16 mRNA and p16 mRNA was clearly observed in the cytoplasm of lymhocytes. p16 expression did not show correlation with such factors as sex, age and immunophenotype in NHL, but there was a significant difference between the pattern of expression of p16 in well differenciated lymphomas and poorly differentiated lymphomas ( P <0.05). Moreover, 42 patients were followed postoperatively for over 3 years, both p16 protein and mRNA correlated with the prognosis of these patients. Conclusion There was a higher incidence of negative expression of p16 mRNA and protein in NHL, which indicates that p16 gene inactivation may play an important role in the genesis and development of some NHL. The frequency of negative expression of p16 mRNA was lower than that of p16 protein suggests that it may be due to post transcriptional regulation or the unsteadiness of mRNA or protein expressed. The positive expression of both p16 mRNA and p16 protein may be features for favorable prognosis in patients with NHL.