淋巴结内外弥漫性大B细胞淋巴瘤p53、p63和PIM1蛋白表达与临床预后的相关性  

Expressions of p53, p63 and PIM1 proteins in nodal or extranodal diffuse large B-cell lymphoma and their prognostic significance

作　　者：陈舒 徐晓莹 雷园园 黄浦 杨鑫 刘岩雪 郭玉虹[1,2] 张艳辉 潘毅 翟琼莉[1,2] 王先火 李兰芳[1,3] 张会来 付凯[1,4] 孟斌 CHEN Shu;XU Xiaoying;LEI Yuanyuan;HUANG Pu;YANG Xin;LIU Yanxue;GUO Yuhong;ZHANG Yanhui;PAN Yi;ZHAI Qiongli;WANG Xianhuo;LI Lanfang;ZHANG Huilai;FU Kai;MENG Bin(Tianjin Medical University Cancer Institute and Hospital,National Clinical Research Center for Cancer,Tianjin Key Laboratory of Cancer Prevention and Therapy,Tianjin’s Clinical Research Center for Cancer,Sino-US Center of Tianjin Medical University Cancer Institute and Hospital for Diagnosis and Treatment on Lymphoma and Leukemia,Tianjin 300060,China;Department of Pathology,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China;Department of Lymphoma,Tianjin Medical University Cancer Institute and Hospital,Tianjin 300060,China;Department of Pathology and Microbiology,University of Nebraska Medical Center,Omaha,NE 68198-3135,USA)

机构地区：[1]天津医科大学肿瘤医院,国家肿瘤临床医学研究中心,天津市肿瘤防治重点实验室,天津市恶性肿瘤临床医学研究中心,天津医科大学肿瘤医院中美淋巴血液肿瘤诊治中心,天津300060 [2]天津医科大学肿瘤医院病理科,天津300060 [3]天津医科大学肿瘤医院淋巴瘤内科,天津300060 [4]美国内布拉斯加大学医学中心病理学与微生物学系,奥马哈NE68198-3135

出　　处：《肿瘤》2019年第11期931-941,共11页Tumor

摘　　要：目的:探讨淋巴结内外弥漫性大B细胞淋巴瘤(diffuse large B-cell lymphoma,DLBCL)中p53、p63和PIM1蛋白表达与患者预后的相关性。方法:采用免疫组织化学法检测p53、p63和PIM1蛋白在淋巴结内外DLBCL中的表达情况。采用χ^2检验分析p53、p63和PIM1在淋巴结内外DLBCL中的表达差异,并用Kaplan-Meier生存曲线及COX风险比例模型分析p53、p63和PIM1表达水平及其他临床病理学特征与淋巴结内外DLBCL患者预后的关系。结果:212例DLBCL患者中,淋巴结内DLBCL有101例,淋巴结外DLBCL有111例(其中55例为胃肠DLBCL,56例为非胃肠DLBCL)。所有DLBCL患者中p53、p63和PIM1蛋白表达率分别为19.0%、25.2%和54.7%;其中,p53蛋白多表达于淋巴结外胃肠管(P <0.05),p63多表达于淋巴结外非胃肠管(P <0.05),而PIM1在各组间表达水平无明显差异(P值均> 0.05)。p53阳性者多为国际预后指数(international prognostic index,IPI)≥3分(P <0.05),p63阳性者多见乳酸脱氢酶(lactate dehydrogenase,LDH)水平升高(P <0.05),而PIM1表达与各临床特征之间无明显相关性(P值均> 0.05)。生存分析显示,p53与淋巴结内病例、p63与淋巴结外非胃肠组病例的总生存期(overall survival,OS)和无进展生存期(progression-free survival,PFS)明显相关(P值均<0.05),而PIM1表达则与淋巴结外胃肠组病例的PFS明显相关(P <0.05)。结论:淋巴结内外不同部位DLBCL的分子发病机制可能存在明显不同,值得进一步深入研究。Objective: To investigate the correlation between the expression of p53, p63 or PIM1 protein and the survival of patients with nodal or extranodal diffuse large B-cell lymphoma(DLBCL).Methods: Immunohistochemical staining was applied to examine the expressions of p53, p63 and PIM1 proteins in nodal or extranodal DLBCL. The differences in the expressions of p53, p63 and PIM1 proteins between nodal and extranodal DLBCL were analyzed by χ^2 test. Kaplan-Meier survival curve and COX proportional hazard model were used to analyze the relationship between the clinicopathological factors(including p53, p63 and PIM1 expressions) and the prognosis of patients with nodal or extranodal DLBCL.Results: Among 212 DLBCL cases, there were 101 nodal cases and 111 extranodal cases(including 55 cases of gastrointestinal DLBCL and56 cases of non-gastrointestinal DLBCL). The expression rates of p53,p63 and PIM1 proteins in all cases were 19.0%, 25.2% and 54.7%,respectively. Among them, p53 was expressed more frequently in extranodal gastrointestinal cases(P < 0.05), p63 was expressed more commonly in extranodal non-gastrointestinal cases(P < 0.05),whereas PIM1 expression was not significant among the three groups(all P > 0.05). Much more p53-positive cases were observed with international prognostic index(IPI) ≥ 3(P < 0.05), while p63-positive patients were more common with elevated lactate dehydrogenase(LDH)(P < 0.05). However, PIM1 expression was not significantly correlated with the clinicopathological factors(all P > 0.05). Survival analysis showed that the expression of p53 or p63 protein was a significant inferior prognostic factor for overall survival(OS) and progression-free survival(PFS) in nodal patients or extranodal non-gastrointestinal DLBCL patients, respectively(both P < 0.05),while PIM1 expression was an inferior prognostic factor for PFS in extranodal gastrointestinal cases(P < 0.05).Conclusion: The molecular mechanisms of DLBCL pathogenesis may be different between different locations of DLBCL, which is worth fur

关 键 词：淋巴瘤 大B细胞 弥漫性 预后 免疫组织化学 肿瘤抑制蛋白质P53 P63蛋白 PIM1蛋白 发病部位 

分 类 号：R733.4[医药卫生—肿瘤]