From the Department of Pathology, Hospital Clínic of Barcelona, Barcelona, Spain (Frigola, Bühler, Marginet, Alamo, Aldecoa, Campo, Balagué).
The Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), Barcelona, Spain (Frigola, Bühler, Enjuanes, Nadeu, Campo, Balagué).
Arch Pathol Lab Med. 2023 Aug 1;147(8):896-906. doi: 10.5858/arpa.2021-0517-OA.
CONTEXT.—: Despite their stromal origin, follicular dendritic cells (FDCs) share many functions with hematopoietic system cells. FDC neoplasms are currently classified by the World Health Organization along with those of a histiocytic nature. However, the molecular alterations driving oncogenesis in FDC sarcomas (FDCSs) are beginning to be unveiled and do not seem to concur with those described in histiocytic neoplasms, namely MAPK pathway activation.
OBJECTIVE.—: To identify molecular alterations driving tumorigenesis in FDCS.
DESIGN.—: We investigated the role of MYC and TP53 in FDC-derived tumor oncogenesis and assessed comprehensively the status of the MAPK pathway in 16 FDCSs, 6 inflammatory pseudotumor (IPT)-like FDCSs, and 8 IPTs.
RESULTS.—: MYC structural alterations (both amplifications and rearrangements) were identified in 5 of 14 FDCSs (35.7%), all associated with MYC overexpression. TP53 mutations were identified in 4 of 14 FDCSs (28.6%), all of which displayed intense and diffuse p53 expression. None of these alterations were identified in any IPT-like FDCSs or in IPT cases. No MAPK pathway gene alterations were identified in any of the cases studied.
CONCLUSIONS.—: The presence of MYC and TP53 alterations and the lack of association with Epstein-Barr virus segregate classical FDCS from IPT-like FDCS, pointing at different oncogenic mechanisms in both entities. Our results suggest a possible oncogenic role of MYC and TP53 alterations in FDCS. The absence of MAPK pathway alterations confirms the lack of a significant role of this pathway in the oncogenesis of FDC-derived neoplasms.
尽管滤泡树突状细胞（FDC）起源于间质，但它们具有许多与造血系统细胞相似的功能。FDC 肿瘤目前与组织细胞来源的肿瘤一起被世界卫生组织分类。然而，推动 FDC 肉瘤（FDCS）发生肿瘤的分子改变开始被揭示，这些改变似乎与组织细胞肿瘤中描述的改变不同，即 MAPK 通路激活。
确定推动 FDCS 肿瘤发生的分子改变。
我们研究了 MYC 和 TP53 在 FDC 来源的肿瘤发生中的作用，并全面评估了 16 例 FDCS、6 例炎性假瘤（IPT）样 FDCS 和 8 例 IPT 中 MAPK 通路的状态。
在 14 例 FDCS 中有 5 例（35.7%）发现了 MYC 结构改变（扩增和重排），均伴有 MYC 过表达。在 14 例 FDCS 中有 4 例（28.6%）发现了 TP53 突变，所有这些突变都显示出强烈和弥漫的 p53 表达。在任何 IPT 样 FDCS 或 IPT 病例中均未发现这些改变。在研究的所有病例中均未发现 MAPK 通路基因改变。
MYC 和 TP53 改变的存在以及与 EBV 无关，将经典 FDCS 与 IPT 样 FDCS 区分开来，表明这两种实体具有不同的致癌机制。我们的结果表明 MYC 和 TP53 改变可能在 FDCS 中具有致癌作用。MAPK 通路改变的缺失证实了该通路在 FDC 来源的肿瘤发生中没有重要作用。
