COX-2,p16INK4A,p53蛋白在经典型霍奇金淋巴瘤患者中的表达及其预后相关分析

Abstract

目的 观察环氧化酶2(COX-2)、周期素依赖激酶抑制剂p16(p16INK4A)、p53蛋白在经典型霍奇金淋巴瘤(cH)患者中的表达,探讨其与患者预后的相关性.方法 收集52例cHL患者的标本,采用免疫组织化学染色法检测相关蛋白,采用原位杂交技术检测EBV及EBV编码的小mRNA(EBER).结合患者临床及随访资料分析COX-2、p16INK4A、p53蛋白表达与预后的相关性.结果 52例患者中男女比例1.6∶1,患者发病年龄22～ 68岁,均为淋巴结内原发.52例患者中COX-2阳性者28例(53.8％),p16INK4A阳性者25例(48.1％),p53阳性者42例(80.8％).按照患者年龄(以中位年龄为界)、性别(男/女)、EBV感染(有/无)、B症状(有/无)及Ann-Arbor分期(Ⅰ～Ⅱ/Ⅲ～Ⅳ期)进行分组,分别与COX-2、p16INK4A、p53表达进行相关性分析,结果显示仅p53表达与Ann-Arbor分期有关(P=0.027).三者间表达的相关性分析结果显示,COX-2表达与p53相关(P=0.008),而与p16INK4A无关(P=0.246),16INK4A与p53表达无关(P=0.958).单因素分析结果显示COX-2表达是影响患者无事件生存(EFS)的不良预后因素(P=0.003);采用COX比例风险回归模型进行多因素分析结果显示COX-2表达是影响患者EFS的独立不良预后因素(HR=0.091,95％CI 0.017～0.505,P=0.006).结论 COX-2、p16INK4A、p53在cHL患者中有较高表达率;与患者EBV感染状态均无相关性;COX-2表达是影响患者EFS的独立不良预后因素.

Objective To investigate the expression level of COX-2,p16INK4A and p53 in patients with classic Hodgkin' s lymphoma (cHL),and to evaluate their correlation with prognosis.Methods The clinical data and samples of 52 cHL cases were collected.Immunohistochemical staining was performed to analyze the proteins level mentioned above and in situ hybridization of EBV encoded RNA (EBER) to clarify the tumor EBV infection state.Correlation between the protein expression and prognosis of patients was analyzed.Results Of 52 cases,the male and female ratio was 1.6∶ 1,the age was from 22 to 68 years old.All lesions located primarily in lymph nodes.All samples from 52 cases were stained with COX-2,p16INK4A and p53,and the positive expression of COX-2 was found in 28 cases (53.8％),that of p16INK4A in 25 cases (48.1％) and p53 in 42 cases (80.8％).All patients were divided into two groups according to differences in age (＜40 years/.≥40years),gender (male/female),EBV infection (yes/no),B symptoms (yes/no),and the Ann Arbor staging (Ⅰ-Ⅱ/Ⅲ-Ⅳ),the correlation with COX-2,p 16INK4A and p53 expression were analyzed,and only p53 expression was correlated with Ann Arbor staging (P=0.027).The statistical analysis of correlations between COX-2,pl6INK4A and p53 showed that the expression of COX-2 was strongly correlated with p53 (P=0.008),and pl6INK4A was not related to either COX-2 or p53 (P=0.246 and 0.958).Kaplan-Meier univariate OS analysis using SPSS17.0 software showed that only COX-2 expression was an adverse prognostic factor for patients' event free survival (EFS) (P=0.003).Meanwhile COX-2 expression was a unique independent prognostic factor analyzed by COX proportional hazards regression model (HR=0.091,95％ CI 0.017-0.505,P=0.006).Conclusion The expression rate of COX-2,p16INK4A and p53 in the cHL were relatively high;and they were not statistically correlated with tumor EBV infection status;the COX-2 positive group had poor prognosis,but only event free survival time becomes statistically significant shorter.COX proportional hazard regression model was used to analyze the COX-2 expression as a independent adverse prognostic factors for EFS.