Department of Pathology and Laboratory Medicine, University of Kansas Medical Center, Kansas City, KS.
Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX.
Clin Lymphoma Myeloma Leuk. 2019 Jul;19(7):e385-e392. doi: 10.1016/j.clml.2019.03.030. Epub 2019 Apr 5.
The Wnt/β-catenin signaling pathway is a major target of p53. β-Catenin/p53 coexpression predicts poorer survival in carcinoma patients. Conversely, CD99 inhibits tumor metastasis through the Wnt/β-catenin pathway. We therefore assessed p53, β-catenin, and CD99 by immunohistochemistry.
We studied 45 patients with systemic anaplastic large-cell lymphoma (ALCL), including 20 anaplastic lymphoma kinase (ALK)-positive and 25 ALK-negative ALCL. β-Catenin expression was analyzed using phospho-β-catenin-S552 antibody because its nuclear localization indicates Wnt signaling.
In this cohort, p53 expression was associated with ALK-negative ALCL. Furthermore, p53 or β-catenin expression alone or β-catenin/p53 double expression showed poorer overall survival and disease-free survival in patients with ALCL overall and in patients with ALK-negative ALCL. CD99 expression was more frequent in ALK-positive ALCL but had no prognostic significance.
This is the first study to evaluate phospho-β-catenin-S552 expression in ALCL. The results of this study, although limited by small patient size, suggest that β-catenin and p53 may play a role in pathogenesis and may be helpful in risk stratification of ALCL patients.
Wnt/β-catenin 信号通路是 p53 的主要靶点。β-catenin/p53 共表达预示着癌患者的生存预后较差。相反,CD99 通过 Wnt/β-catenin 通路抑制肿瘤转移。因此,我们通过免疫组织化学评估了 p53、β-catenin 和 CD99。
我们研究了 45 例系统性间变性大细胞淋巴瘤(ALCL)患者,包括 20 例间变性淋巴瘤激酶(ALK)阳性和 25 例 ALK 阴性 ALCL。β-catenin 的表达使用磷酸化-β-catenin-S552 抗体进行分析,因为其核定位表明存在 Wnt 信号通路。
在本队列中,p53 的表达与 ALK 阴性 ALCL 相关。此外,p53 或β-catenin 单独表达或β-catenin/p53 双表达在 ALCL 患者和 ALK 阴性 ALCL 患者中均显示出较差的总生存期和无病生存期。CD99 的表达在 ALK 阳性 ALCL 中更为频繁,但无预后意义。
这是首次评估 ALCL 中磷酸化-β-catenin-S552 的表达。尽管患者数量较少,但本研究结果表明,β-catenin 和 p53 可能在发病机制中发挥作用,并有助于 ALCL 患者的风险分层。