Histopathologic Features Associated with Molecular Subtypes of Extranodal NK/T Cell Lymphoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K06883
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49020:Human pathology-related
• Research Institution: University of Yamanashi
• Principal Investigator: Oishi Naoki 山梨大学, 大学院総合研究部, 准教授 (90623661)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: NK/T細胞リンパ腫 / 分子病理学 / 遺伝子異常 / BCOR / TP53 / JAK/STAT

Outline of Final Research Achievements

Background: Extranodal NK/T-cell lymphoma (ENKTL) is an Epstein-Barr virus-positive aggressive lymphoma. Pathological risk factors remain to be elucidated. We collected 71 ENKTLs. Immunohistochemistry (IHC) for MYC, pSTAT3, and CD30 was performed. Targeted sequencing for 29 genes was carried out in 67 ENKTLs. Median age was 66 (range, 6-100) years. Targeted sequencing identified mutations including STAT3 (27%), JAK3 (4%), KMT2D (19%), TP53 (13%), BCOR (10%), DDX3X (7%). STAT3 mutation was associated with higher pSTAT3 and CD30 expression by IHC. Univariate analysis showed that stage 2/3/4, BCOR and TP53 mutations, and high MYC expression were associated with reduced overall survival, and multivariate model identified stage 2/3/4, no treatment, and high MYC expression to be an independent prognostic factor. Collectively, high MYC protein expression is an independent adverse prognostic factor for patients with ENKTL.

Free Research Field

リンパ腫

Academic Significance and Societal Importance of the Research Achievements

節外性NK/T細胞リンパ腫は予後不良かつ希少なリンパ腫であり，病理学的に評価可能な予後因子の同定が求められています。本研究で、MYC蛋白を過剰に発現する節外性NK/T細胞リンパ腫は全生存期間が短く，遺伝子異常のパターンも異なることがわかりました。MYC蛋白の発現は免疫組織化学という方法で比較的簡便に調べることができ、実臨床ですぐに応用可能なバイオマーカーとして期待されます。