磷酸化 STAT3 作为 ALK ALCL 与 CD30 PTCL、NOS 相比的潜在诊断和预测生物标志物。
Phosphorylated STAT3 as a potential diagnostic and predictive biomarker in ALK ALCL vs. CD30 PTCL, NOS.
机构信息
Department of Pathology, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Department of Pathology, Xuzhou Medical University, Xuzhou, China.
出版信息
Front Immunol. 2023 Jun 14;14:1132834. doi: 10.3389/fimmu.2023.1132834. eCollection 2023.
AIMS
The differential diagnosis between ALK-negative anaplastic large cell lymphoma (ALK ALCL) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) with high expression of CD30 (CD30) are essential. However, no reliable biomarker is available in daily practice except CD30. STAT3 is characteristically activated in ALCL. We aimed to investigate whether the status of STAT3 phosphorylation could help the differential diagnosis.
METHODS
The status of phosphorylation of STAT3 was examined using two antibodies against pSTAT3-Y705 and pSTAT3-S727 by immunohistochemistry in ALK ALCL (n=33), ALK ALCL (n=22) and PTCL, NOS (n=34). Ten PTCL, NOS with diffuse CD30 expression were defined as CD30 PTCL, NOS. Flowcytometric analysis were performed to evaluate the expression of pSTAT3-Y705/S727 in PTCL, NOS (n=3).
RESULTS
The median H-scores of pSTAT3-Y705 and S727 were 280 and 260 in ALK ALCL, 250 and 240 in ALK ALCL, and 45 and 75 in CD30 subgroup, respectively. Using H score of 145 as the cutoff value, pSTAT3-S727 alone distinguished between ALK ALCL and CD30 PTCL, NOS with a sensitivity of 100% and specificity of 83%. Additionally, pSTAT3-S727, but not pSTAT3-Y705, was also expressed by background tumor-infiltrating lymphocytes (S727) in PTCL, NOS. PTCL, NOS patients with high S727 H score had a favorable prognosis than those with no TILs (3-year OS rate: 43% vs. 0, =0.013) or low S727 (3-year OS rate: 43% vs. 0, =0.099). Flowcytometric analysis revealed that of the three patients investigated, two had enhanced pSTAT-S727 signals in neoplastic cell populations, and all three patients were negative for pSTAT3-Y705 expression in both tumor cells and background lymphocytes.
CONCLUSIONS
pSTAT3-Y705/S727 can be used to help distinguish ALK ALCL from CD30 PTCL, NOS and pSTAT3-S727 expression by TILs predicts the prognosis of a subset of PTCL, NOS.
目的
ALK 阴性间变性大细胞淋巴瘤（ALK ALCL）与高表达 CD30（CD30）的外周 T 细胞淋巴瘤，非特指型（PTCL，NOS）的鉴别诊断至关重要。然而，除了 CD30 之外，在日常实践中尚无可靠的生物标志物。STAT3 在 ALCL 中特征性地被激活。我们旨在研究 STAT3 磷酸化状态是否有助于鉴别诊断。
方法
通过免疫组化法检测 33 例 ALK ALCL、22 例 ALK ALCL 和 34 例 PTCL，NOS 中 pSTAT3-Y705 和 pSTAT3-S727 两种针对 pSTAT3-Y705 和 pSTAT3-S727 的抗体的磷酸化状态。对 10 例弥漫性 CD30 表达的 PTCL，NOS 定义为 CD30 PTCL，NOS。对 3 例 PTCL，NOS 进行流式细胞术分析，评估 pSTAT3-Y705/S727 的表达。
结果
ALK ALCL 的 pSTAT3-Y705 和 S727 的中位数 H 评分分别为 280 和 260，ALK ALCL 的中位数 H 评分分别为 250 和 240，CD30 亚组的中位数 H 评分为 45 和 75。使用 145 作为截断值，pSTAT3-S727 单独用于区分 ALK ALCL 和 CD30 PTCL，NOS，其灵敏度为 100%，特异性为 83%。此外，PTCL，NOS 中的背景肿瘤浸润淋巴细胞（S727）也表达 pSTAT3-S727，而非 pSTAT3-Y705。高 S727 H 评分的 PTCL，NOS 患者的预后优于无 TILs（3 年 OS 率：43%与 0，=0.013）或低 S727（3 年 OS 率：43%与 0，=0.099）的患者。流式细胞术分析显示，在 3 例研究患者中，有 2 例在肿瘤细胞群中增强了 pSTAT-S727 信号，所有 3 例患者的肿瘤细胞和背景淋巴细胞均无 pSTAT3-Y705 表达。
结论
pSTAT3-Y705/S727 可用于帮助鉴别 ALK ALCL 与 CD30 PTCL，NOS，并且 TILs 表达的 pSTAT3-S727 预测了一部分 PTCL，NOS 的预后。
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