关键词: Mib1/Ki67 index Yamanaka factors cancer stem cell multinucleated giant cell plasmablastic neoplasm

来  源:   DOI:10.3389/fonc.2022.1023785   PDF(Pubmed)

Abstract:
Cancer stem cells have the capability of self-renewal and multipotency and are, therefore, associated with tumor heterogeneity, resistance to chemoradiation therapy, and metastasis. The hypothesis that multinucleated giant cells, which often emerge following chemo- and/or radiotherapy, serve as cancer stem cells has not been fully evaluated. Although a previous study demonstrated that these cells functioned as stem cells, only low levels of Yamanaka factors were expressed, contrasting with the high expression seen from their gestated first-generation mononuclear cells. Herein, we report a case of a plasmablastic neoplasm with multinucleated giant cells that were analyzed for stemness to test the above hypothesis. The patient was a male in his 80s who had a plasmablastic neoplasm that was not easily distinguishable as plasmablastic lymphoma versus plasma cell myeloma of plasmablastic type. Lymph node biopsy showed predominant mononuclear cell proliferation with admixed multinucleated giant cells. Immunohistochemistry and in situ hybridization showed that both multinucleated and mononuclear cells had the same profile: CD138(+), light chain restriction of κ>λ, cyclin D1(+), CD68(-), EBER-ISH (+). These results suggested that both cell types were neoplastic. In accordance with the previous study, the multinucleated giant cells showed low expression of Yamanaka factors, which were highly expressed in some of the mononuclear cells. Furthermore, the multinucleated giant cells showed a much lower proliferative activity (Mib1/Ki67 index) than the mononuclear cells. Based on these results, the multinucleated giant cells were compatible with cancer stem cells. This case is expected to expand the knowledge base regarding biology of cancer stem cells.
摘要:
肿瘤干细胞具有自我更新和多潜能的能力,因此,与肿瘤异质性相关,对放化疗的抗性,和转移。假设多核巨细胞,通常在化疗和/或放疗后出现,作为癌症干细胞尚未得到充分评估。尽管先前的研究表明这些细胞具有干细胞的功能,只有低水平的山中因子被表达,与妊娠第一代单核细胞的高表达相反。在这里,我们报道了一例具有多核巨细胞的浆细胞性肿瘤,对其进行了干性分析以检验上述假设。该患者是80多岁的男性,患有浆细胞性肿瘤,不易区分为浆细胞性淋巴瘤和浆细胞性浆细胞性骨髓瘤。淋巴结活检显示主要的单核细胞增殖与混合的多核巨细胞。免疫组织化学和原位杂交显示多核和单核细胞具有相同的谱:CD138(+),κ>λ的轻链限制,细胞周期蛋白D1(+),CD68(-),EBER-ISH(+)。这些结果表明两种细胞类型都是肿瘤。根据之前的研究,多核巨细胞显示Yamanaka因子的低表达,在一些单核细胞中高度表达。此外,多核巨细胞的增殖活性(Mib1/Ki67指数)远低于单核细胞。基于这些结果,多核巨细胞与癌症干细胞相容。预计该病例将扩大有关癌症干细胞生物学的知识库。
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