1st Department of Pathology and Experimental Cancer Research, Faculty of Medicine, Semmelweis University, Üllői út 26, 1085, Budapest, Hungary.
Virchows Arch. 2014 Feb;464(2):229-39. doi: 10.1007/s00428-013-1519-9. Epub 2013 Dec 4.
Primary bone lymphoma (PBL) comprises 5 % of all extranodal non-Hodgkin's lymphomas (NHLs). Diffuse large B-cell lymphoma (DLBCL) accounts for the majority of cases, which is the most heterogeneous group of lymphomas. Previous studies suggested that besides the tumor cell phenotype, phosphatidylinositol 3-kinase/acutely transforming retrovirus/mammalian target of rapamycin (PI3K/AKT/mTOR) pathway activity and the composition of the immune-microenvironment of DLBCL influence the clinical behavior of the disease. The aim of our study was to determine the relationship between clinical factors, tumor cell phenotype, microenvironment, PI3K/AKT/mTOR pathway activity, and disease outcome in primary bone diffuse large B-cell lymphoma (PB-DLBCL). We constructed tissue-microarrays from 41 cases of PB-DLBCL. To characterize tumor cell phenotype, T-cell subsets, macrophages, and PI3K/AKT/mTOR pathway activity immunohistochemical stainings were evaluated. Kaplan-Meier survival analysis provided evidence that age (≤65), CD3 and CD8+ T cell infiltrations >5 %, low BCL2 expression of the tumor cells (≤30 %), and low proliferation index (Ki67 ≤ 57 %) were associated with favorable outcome of PB-DLBCL patients. Multivariate analysis revealed that CD8+ T cell infiltration >5 % and low BCL2 expression (≤30 %) were independent predictors of survival. Increased macrophage infiltration (>10 %) showed tendency toward an adverse prognostic effect. International prognostic index, tumor cell phenotype (GCB or ABC), MYC protein expression, and activation of PI3K/AKT/mTOR pathway had no significant impact on survival. However, mTOR activity showed a significant correlation with activated B-cell phenotype. We conclude that CD8 and BCL2 expressions are potential prognostic markers for PB-DLBCL patients and the PI3K/AKT/mTOR pathway appears to be an additional therapeutic target in PB-DLBCL with activated-B-cell phenotype.
原发性骨淋巴瘤（PBL）占所有结外非霍奇金淋巴瘤（NHL）的 5%。弥漫性大 B 细胞淋巴瘤（DLBCL）占大多数病例，是淋巴瘤中最具异质性的一组。先前的研究表明，除了肿瘤细胞表型外，磷脂酰肌醇 3-激酶/急性转化逆转录病毒/哺乳动物雷帕霉素靶蛋白（PI3K/AKT/mTOR）通路活性和 DLBCL 的免疫微环境组成影响疾病的临床行为。我们的研究旨在确定原发性骨弥漫性大 B 细胞淋巴瘤（PB-DLBCL）中的临床因素、肿瘤细胞表型、微环境、PI3K/AKT/mTOR 通路活性与疾病结局之间的关系。我们从 41 例 PB-DLBCL 病例中构建了组织微阵列。为了描述肿瘤细胞表型，评估了 T 细胞亚群、巨噬细胞和 PI3K/AKT/mTOR 通路活性的免疫组织化学染色。Kaplan-Meier 生存分析表明，年龄（≤65 岁）、肿瘤细胞 CD3 和 CD8+T 细胞浸润>5%、低 BCL2 表达（≤30%）和低增殖指数（Ki67≤57%）与 PB-DLBCL 患者的良好预后相关。多变量分析显示，CD8+T 细胞浸润>5%和低 BCL2 表达（≤30%）是生存的独立预测因素。巨噬细胞浸润增加（>10%）显示出不良预后的趋势。国际预后指数、肿瘤细胞表型（GCB 或 ABC）、MYC 蛋白表达和 PI3K/AKT/mTOR 通路的激活对生存没有显著影响。然而，mTOR 活性与活化 B 细胞表型显著相关。我们得出结论，CD8 和 BCL2 表达是 PB-DLBCL 患者的潜在预后标志物，PI3K/AKT/mTOR 通路似乎是具有活化 B 细胞表型的 PB-DLBCL 的另一个治疗靶点。
