PDGFRA和CMYC在结外NK/T细胞淋巴瘤中的表达及预后相关因素探讨

Expression of PDGFRA and CMYC in extranodal NK/T-ceii lymphoma and their prognostic implications

目的探讨结外NK/T细胞淋巴瘤（extranodal NK/T－cell lymphoma, ENKTL）中PDGFRA和CMYC蛋白表达及其与临床病理特征及预后的关系。方法收集54例ENKTL石蜡标本，采用免疫组织化学的方法检测CD20、CD2、CD3、CD56、T细胞胞质内抗原（TIA）1、颗粒酶B、Ki－67、PDGFRA和CMYC等蛋白的表达，原位杂交检测EB病毒编码的小RNA（EBER），用50例鼻咽黏膜淋巴组织增生的标本作为正常对照组。结果（1）54例ENKTL中，CD20全部阴性，CD3、CD2、TIA1、颗粒酶B全部阳性，81.0%（47/54）CD56阳性，83.3%（45/54）Ki－67〉60%阳性。EBER原位杂交全部阳性（100%）。（2）PDGFRA和CMYC蛋白阳性表达率分别为51.9%（28/54）和53.7%（29/54），均高于鼻咽黏膜淋巴组织增生标本中的表达率0（P值均〈0.05）。PDGFRA和CMYC蛋白在ENKTL中的表达呈正相关（r=0.295，P〈0.05）。（3）CMYC蛋白表达与患者的性别、年龄、临床分期、B症状以及治疗方案无关（P〉0.05），与临床疗效显著相关（P〈0.05）；PDGFRA蛋白表达与患者的性别、年龄、临床分期、治疗方案以及临床疗效无关（P〉0.05），与B症状显著相关（P〈0.05）；PDGFRA和CMYC蛋白同时表达与患者的性别、年龄、临床分期、B症状、治疗方案以及临床疗效均无相关性（P〉0.05）。（4）单因素生存分析显示，临床分期、CMYC蛋白及PDGFRA和CMYC蛋白同时表达与ENKTL的预后相关，而性别、年龄、B症状、治疗方案、疗效和PDGFRA蛋白与预后差异无统计学意义（P〉0.05）。进一步多因素COX分析结果显示：临床分期、CMYC蛋白阳性表达及PDGFRA和CMYC蛋白同时表达可作为ENKTL独立的预后因子（P〈0.05）。结论PDGFRA和CMYC在ENKTL中高表达，CMYC蛋白阳性表达及PDGFRA和CMYC蛋白同时表达可作为ENKTL独立的预后因子、评估预后，提示有风险。

Objective To investigate the relationship between expression of PDGFRA/CMYC and clinicopathologic features of extranodal NK/T-cell lymphoma. Methods Fifty-four cases of extranodal NK/ T-cell lymphoma were included in the study. Immunohistochemistry was used to detect the expression of CD20, CD2, CD3, CD56, TIA1 ,GrB, Ki-67, PDGFRA and CMYC. In situ hybridization was performed to detect the presence of EBV encoded small RNA （EBER）. Fifty cases of nasopharyngeal mucosal lymphoid tissue hyperplasia were used as normal control. Results Among 54 cases of ENKTL,CD2, CD3, GrB, and TIA1 were expressed in all the tumors. CD56 was expressed in 47 cases （81.0%） and CD20 was not detectable in any cases. Ki-67 proliferative index expression of 〉 60% was found in 45 cases （83.3%）. In situ hybridization for EBER was positive in all cases （ 100% ）. The positive expression rates of PDGFRA and CMYC in extranodal NK/T-cell lymphomas were 51.9% （28/54） and 53.7% （29/54）, respectively, much higher than those in nasopharyngeal mucosal lymphoid tissue hyperplasia （ 0, P 〈 0. 05 ） . There was a positive correlation between PDGFRA and CMYC （r = 0. 295, P 〈 0. 05 ）. The expression of CMYC was correlated with clinical efficacy （ P 〈 0. 05 ） , but not with gender, age, Ann Arbor stage, B symptoms and therapeutic regimen （ all P 〉 0. 05 ）. The expression of PDGFRA was correlated with B symptoms （ P 〈 0. 05 ） , while not with gender, age, Ann Arbor stage, therapeutic regimen and clinical efficacy （ all P 〉 0.05 ）. The co-expression of PDGFRA and CMYC was not correlated with gender, age, Ann Arbor stage, B symptoms, therapeutic regimen and clinical efficacy （ P 〉 0. 05 ）. Univariate analysis showed that the stage, clinical efficacy, CMYC protein and the co-expression of PDGFRA and CMYC were significantly correlated with the prognosis. The overall survival of the patients with CMYC positive expression was shorter than of that of the patients with negative expression （P 〈 0. 05 ）. Multivariable Cox regression analysis further confirmed that clinical stage, CMYC protein expression, and the co-expression of PDGFRA and CMYC were independent prognostic factors in patients with extranodal NIL/T-cell lymphoma. Conclusion CMYC protein, and the co-expression of PDGFRA and CMYC can be as an independent prognostic factor in patients with extranodal NK/T-cefl lymphoma and influence the prognosis of patients.