Department of Medical Biotechnologies, Section of Pathology, University of Siena, 53100, Siena, Italy.
Department of Histopathology, University College London, University College Hospital, Rockefeller Building, UCL Site, 21 University Street, London, WC1E 6JJ, UK.
Virchows Arch. 2018 Dec;473(6):749-757. doi: 10.1007/s00428-018-2434-x. Epub 2018 Aug 27.
Granulysin is a cytolytic protein expressed in cytotoxic T and natural killer (NK) cells. Abnormal serum levels of granulysin in lymphomas with NK and cytotoxic phenotype have been shown to correlate with tumour progression. In this study, we investigated the expression pattern of granulysin in routine sections of normal and reactive lymphoid tissues as well as in a large series of lymphomas. In normal tissues, granulysin labelled a small population of cells that double immunostaining revealed to belong to the pool of cytotoxic T/NK cells. Among lymphoid neoplasms, the highest expression of granulysin (71%) was found in extranodal NK/T cell lymphomas of nasal type (ENKTL). To note is that 29% of ENKTLs, which were negative for one or more of classical cytotoxic markers strongly expressed granulysin. Furthermore, expression of granulysin was observed in rare cases of T cell lymphomas with a cytotoxic phenotype (i.e. ALK-negative anaplastic large cell lymphoma (26%), enteropathy-associated T cell lymphoma (12%) and peripheral T cell lymphoma, NOS (4%)). None of the investigated non-Hodgkin B cell lymphomas, Hodgkin lymphoma and plasma cell myeloma were granulysin positive. The results suggest granulysin as a novel marker for a subset of cytotoxic NK cell derived malignancies and its usefulness is highlighted in those ENKTLs that lack expression of other cytotoxic markers but retain granulysin expression.
颗粒酶是一种在细胞毒性 T 细胞和自然杀伤 (NK) 细胞中表达的细胞溶解蛋白。具有 NK 和细胞毒性表型的淋巴瘤中异常的血清颗粒酶水平与肿瘤进展相关。在这项研究中,我们研究了颗粒酶在正常和反应性淋巴组织的常规切片以及一系列大系列淋巴瘤中的表达模式。在正常组织中,颗粒酶标记了一小部分细胞,双免疫染色显示这些细胞属于细胞毒性 T/NK 细胞池。在淋巴肿瘤中,颗粒酶表达最高(71%)的是结外 NK/T 细胞淋巴瘤,鼻型(ENKTL)。值得注意的是,29%的 ENKTL 缺乏一种或多种经典细胞毒性标志物,但强烈表达颗粒酶。此外,在具有细胞毒性表型的 T 细胞淋巴瘤(即ALK 阴性间变性大细胞淋巴瘤(26%)、肠病相关 T 细胞淋巴瘤(12%)和外周 T 细胞淋巴瘤,NOS(4%))中也观察到颗粒酶的表达。所研究的非霍奇金 B 细胞淋巴瘤、霍奇金淋巴瘤和浆细胞瘤均为颗粒酶阴性。这些结果表明,颗粒酶是一组新型的细胞毒性 NK 细胞衍生恶性肿瘤的标志物,对于缺乏其他细胞毒性标志物表达但保留颗粒酶表达的那些 ENKTL 尤其有用。