The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma
The Positivity of Phosphorylated STAT3 Is a Novel Marker for Favorable Prognosis in Germinal Center B-Cell Type of Diffuse Large B-Cell Lymphoma
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DOI：
10.1097/pas.0000000000001691
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发表时间：
2021-06-01
影响因子：
5.6
通讯作者：
Masuzaki，Hiroaki
中科院分区：
文献类型：
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作者：
Morichika，Kazuho;Karube，Kennosuke;Masuzaki，Hiroaki
根据免疫组织化学，弥漫性大B细胞淋巴瘤（DLBCL）分为生殖中心B细胞（GCB）或非GCB亚型。最近的整合基因组分析强调了JAK-STAT 3通路在DLBCL分子发病机制中的重要性。然而，其与临床结局的相关性仍存在争议。因此，我们通过免疫组织化学评估了磷酸化STAT 3（pSTAT 3）的核表达程度，pSTAT 3是信号转导和转录激活因子3（STAT 3）激活的替代标记物。我们还分析了294例DLBCL患者中pSTAT 3阳性（定义为≥ 40%阳性肿瘤细胞）与临床病理特征之间的潜在关系。pSTAT 3在122例（42%）患者中检测到，非GCB亚型中的阳性率高于GCB亚型（57% vs. 28%，P< 0.001）。在pSTAT 3阳性非GCB亚型中鉴定出潜在激活STAT 3、MYD 88 L265 P和EB病毒编码的小RNA的因子，而pSTAT 3阳性GCB亚型通常显示STAT 3突变，缺乏EZH 2突变和BCL 2和MYC重排。多变量分析显示，pSTAT 3阳性GCB亚型显示出良好的预后（HR：0.17; 95%置信区间，0.04-0.7; P= 0.014）。这些发现表明，pSTAT 3阳性可能对DLBCL的临床病理特征具有独特的影响，使其成为GCB亚型患者良好预后的有前途的新标志物。
On the basis of immunohistochemistry, diffuse large B-cell lymphoma (DLBCL) is categorized as a germinal center B-cell (GCB) or non-GCB subtype. Recent integrated genomic analyses have highlighted the importance of the JAK-STAT3 pathway in the molecular pathogenesis of DLBCL. However, its relevance to clinical outcomes remains controversial. Therefore, we evaluated the extent of the nuclear expression of phosphorylated STAT3 (pSTAT3), a surrogate marker of signal transducer and activator of transcription 3 (STAT3) activation, by immunohistochemistry. We also analyzed the potential relationship between pSTAT3 positivity (defined as≥ 40% positive neoplastic cells) and clinicopathologic characteristics in 294 patients with DLBCL. pSTAT3 was detected in 122 patients (42%), with a higher rate in the non-GCB subtype than in the GCB subtype (57% vs. 28%, P< 0.001). Factors potentially activating STAT3, MYD88 L265P, and Epstein-Barr virus-encoded small RNA were identified in the pSTAT3-positive non-GCB subtype, whereas the pSTAT3-positive GCB subtype often showed STAT3 mutations and lacked EZH2 mutations and the rearrangements of BCL2 and MYC. Multivariate analyses revealed that the pSTAT3-positive GCB subtype showed a favorable prognosis (HR: 0.17; 95% confidence interval, 0.04-0.7; P= 0.014). These findings suggest that pSTAT3 positivity may have a unique impact on the clinicopathologic characteristics of DLBCL, making it a promising novel marker for the favorable prognosis of patients with the GCB subtype.