Objective: To screen and analyze the prognostic protein biomarkers of DLBCL, and to explore their value in the prognostic evaluation. Methods: 163 cases of confirmed DLBCLs from January 2011 to December 2016 were collected with their clinical, pathological and follow-up data, which were all from our hospital. The expression of protein markers were tested using immunohistochemical staining (IHC) . The immune phenotypes independent of the International Prognostic Index (IPI) that affect overall survival (OS) and progression-free survival (PFS) of DLBCL were explored by COX regression model, and the effect of their co-expression on the prognosis were also analyzed. Result: BCL6 negative (PFS: HR=1.652, 95%CI 1.030-2.649, P=0.037) , P53 positive (OS: HR=1.842, 95%CI 1.008-3.367, P=0.047) , and BCL2 strong positive expressions (S+) (OS: HR=2.102, 95%CI 1.249-3.537, P=0.005; PFS: HR=2.126, 95%CI 1.312-3.443, P=0.002) are adverse prognostic factors of DLBCL that are independent of IPI. BCL6(-) (PFS: HR=2.042, 95%CI 1.021-4.081, P=0.043) , P53(+) (OS: HR=3.069, 95%CI 1.244-7.569, P=0.015) and BCL2(S+) (OS: HR=2.433, 95%CI 1.165-5.082, P=0.018; PFS: HR=3.209, 95%CI 1.606-6.410, P=0.001) are adverse prognostic factors in the group of age≤60-year-old; in the group of IPI score 0-2, cases with BCL6(-) (OS: HR=2.467, 95%CI 1.322-4.604, P=0.005; PFS: HR=2.248, 95%CI 1.275-3.965, P=0.005) and BCL2(S+) (PFS: HR=2.045, 95%CI 1.119-3.735, P=0.020) have worse prognosis. The co-expression of BCL6(-) and BCL2(S+) has significant influence on prognosis of DLBCL (P=0.005 and P<0.001) , in which BCL6(+)/non-BCL2(S+) (n=86) has the best prognosis[3-year-OS (71.6±4.9) %, 3-year-PFS (67.0±5.1) %], and BCL6(-)/BCL2(S+) (n=10) has the worst prognosis[3-year-OS (20.0±12.6) %, 3-year-PFS (10.0±9.5) %]; the co-expression of BCL6(-) and P53(+) has no significant influence on prognosis (P=0.061 and P=0.089) , however, those cases with BCL6(+)/P53(-) (n=98) often get better prognosis[3-year-OS (70.6±4.7) %, 3-year-PFS (64.6±4.9) %] than others; the co-expression of P53(+) and BCL2(S+) has significant influence on prognosis of DLBCL (P<0.001 and P<0.001) , and P53(+)/BCL2(S+) (n=5) has the worst prognosis (3-year-OS and 3-year-PFS are both 0) ; BCL2(S+) cases get shorter OS and PFS, regardless of the expression of BCL6 and P53. Conclusion: The expression and co-expression of BCL6 negative, P53 positive and BCL2(S+) have certain value in the prognostic evaluation of DLBCL, especially in the group of age≤60-year-old and IPI score 0-2.
目的： 筛选并分析与弥漫大B细胞淋巴瘤（DLBCL）预后相关的免疫表型，探究其预后价值。 方法： 选取天津医科大学肿瘤医院2011年1月至2016年12月收治的163例DLBCL患者，免疫组织化学染色检测DLBCL常见免疫表型，COX模型探索独立于国际预后指数（IPI）影响总生存（OS）与无进展生存（PFS）的免疫表型，并分析其两两联合表达对预后的影响。 结果： 多因素分析显示BCL6阴性（PFS：HR=1.652，95%CI 1.030~2.649，P=0.037）、P53阳性（OS：HR=1.842，95%CI 1.008~3.367，P=0.047）、BCL2强阳性（OS：HR=2.102，95%CI 1.249~3.537，P=0.005；PFS：HR=2.126，95%CI 1.312~3.443，P=0.002）是DLBCL中独立于IPI的预后不良因素。亚组分析显示，在年龄≤60岁组患者中BCL6阴性（PFS：HR=2.042，95%CI 1.021~4.081，P=0.043）、P53阳性（OS：HR=3.069，95%CI 1.244~7.569，P=0.015）和BCL2强阳性（OS：HR=2.433，95%CI 1.165~5.082，P=0.018；PFS：HR=3.209，95%CI 1.606~6.410，P=0.001）对预后影响显著；在IPI 0~2分亚组患者中，BCL6阴性（OS：HR=2.467，95%CI 1.322~4.604，P=0.005；PFS：HR=2.248，95%CI 1.275~3.965，P=0.005）和BCL2强阳性（PFS：HR=2.045，95%CI 1.119~3.735，P=0.020）对预后影响显著。BCL6和BCL2强阳性的联合表达与DLBCL的预后相关（P=0.005和P<0.001），BCL6阳性/BCL2非强阳性（86例）预后最好[3年OS率（71.6±4.9）%，3年PFS率（67.0±5.1）%]，BCL6阴性/BCL2强阳性（10例）预后最差[3年OS率（20.0±12.6）%，3年PFS率（10.0±9.5）%]；BCL6、P53的联合表达与DLBCL的预后差异无统计学意义（P=0.061和P=0.089），但生存曲线显示BCL6阳性/P53阴性的病例（98例）预后较好[3年OS率（70.6±4.7）%，3年PFS率（64.6±4.9）%]；BCL2强阳性、P53的联合表达与DLBCL的预后显著相关（P<0.001和P<0.001），BCL2强阳性/P53阳性的病例（5例）预后最差（3年OS率和PFS率均为0）；无论BCL6与P53表达如何，BCL2强阳性的病例预后均比非强阳性病例差。 结论： BCL6阴性、P53阳性、BCL2强阳性三种免疫表型单独及联合表达对DLBCL尤其是年龄≤60岁和IPI 0~2分患者的预后预测具有一定价值。.
Keywords: BCL2; BCL6; Diffuse large B-cell lymphoma; P53; Prognosis.