JAK/STAT3 Signaling Activation Related to Distinct Clinicopathologic Features in Systemic ALK− Anaplastic Large Cell Lymphomas: New Insights into Their Heterogeneity. (1st January 2023)

• Record Type: Journal Article
• Authors: Wang, Jian-chao; Zhong, Li-hua; Lin, Wei-qing; Zhang, Wen-fang; Xi, Yan-feng; Liu, Yue-ping; Zhu, Qiong; Liu, Wei; Zhu, Wei-feng; Chen, Yan-ping; Chen, Gang
• Is Part Of: American journal of surgical pathology. Volume 47:Number 1(2023)
• Page Start: 55
• Page End: 64
• Publication Date: 2023-01-01
• Subjects: ALK− anaplastic large cell lymphoma -- p-STAT3 -- DUSP22 -- heterogeneity; Pathology, Surgical -- Periodicals; 617.0705
• DOI: 10.1097/PAS.0000000000001995
• Languages: English
• ISSNs: 0147-5185

Abstract

Abstract : Systemic anaplastic lymphoma kinase (ALK)-negative anaplastic large cell lymphoma (ALCL) is a group of heterogenous CD30 + T-cell non-Hodgkin lymphomas. Previous studies have highlighted the importance of JAK/STAT3 signaling activation in the molecular pathogenesis of ALK − ALCLs. In the present study, we aimed to establish a potential relationship between JAK/STAT3 signaling activation and clinicopathologic features in ALK − ALCLs, and further recognize the heterogenous nature of these neoplasms. Immunohistochemistry staining of the phosphorylated-STAT3 (p-STAT3) and dual-specificity protein phosphatase 22 ( DUSP22 ) gene rearrangement analysis were performed. Forty-five cases of ALK − ALCL were divided into 3 groups, including 9 DUSP22 -rearranged ALCLs, 21 p-STAT3 + double-negative (DN) ALCLs (both ALK and DUSP22 rearrangement negative), and 15 p-STAT3 − DN-ALCLs. Morphologically, p-STAT3 + DN-ALCLs exhibited sheet-like neoplastic cells and sometimes showed large pleomorphic cells scattered in a lymphocyte-rich background more frequently than those in other ALK − ALCLs subtypes. Phenotypically, the p-STAT3 + DN-ALCLs frequently expressed cytotoxic molecules, epithelial membrane antigen, and programmed death-ligand 1, whereas CD3 and CD5 expression was not observed. Clinically, patients with p-STAT3 + DN-ALCLs had a better prognosis than those with p-STAT3 − DN-ALCLs. These observations suggest that p-STAT3 + DN-ALCLs represent a distinct subtype of ALK − ALCLs. Identifying ALK − ALCL subtypes by using p-STAT3 staining and DUSP22 rearrangement is a promising approach that may contribute to risk stratification and better treatment decisions in the future clinical practice.