Andersen Maja D, Kamper Peter, Nielsen Patricia S, Bendix Knud, Riber-Hansen Rikke, Steiniche Torben, Hamilton-Dutoit Stephen, Clausen Michael, d'Amore Francesco
Department of Hematology, Aarhus University Hospital, Aarhus, Denmark.
Institute of Pathology, Aarhus University Hospital, Aarhus, Denmark.
Eur J Haematol. 2016 Mar;96(3):252-9. doi: 10.1111/ejh.12583. Epub 2015 Jun 8.
The tumour microenvironment in classical Hodgkin's lymphoma (cHL) is characterised by a minor population of neoplastic Hodgkin and Reed-Sternberg cells within a heterogeneous background of non-neoplastic bystanders cells, including mast cells. The number of infiltrating mast cells in cHL has been reported to correlate with poor prognosis. We used immunohistochemistry to assess the degree of tumour-infiltrating mast cells in cHL tissue microarrays and correlated this with clinico-pathological features and prognosis in a cohort of homogeneously treated patients with Hodgkin's disease. A high degree of tumour mast cells was associated with nodular sclerosis (NS) subtype histology (P = 0.0002). Moreover, the number of mast cells was inversely correlated with the numbers of CD68+ and CD163+ macrophages (P = 0.0001 and P = 0.003, respectively) and with the number of granzyme+ cytotoxic cells (P = 0.004). The degree of mast cell infiltration was not a prognostic factor in cHL of nodular sclerosis subtype. In contrast, in mixed cellularity cHL a high number of intratumoral mast cells correlated with significantly poorer outcome both in terms of overall (P = 0.03) and event-free survival (P = 0.01). Further studies are warranted into the biological mechanisms underlying this adverse outcome and their possible therapeutic implications.
经典型霍奇金淋巴瘤(cHL)的肿瘤微环境特征为,在包括肥大细胞在内的非肿瘤旁观者细胞构成的异质性背景中,存在少量肿瘤性霍奇金和里德-斯腾伯格细胞。据报道,cHL中浸润性肥大细胞的数量与预后不良相关。我们采用免疫组织化学方法评估cHL组织微阵列中肿瘤浸润肥大细胞的程度,并将其与一组接受同质化治疗的霍奇金病患者的临床病理特征及预后进行关联分析。高度的肿瘤肥大细胞与结节硬化(NS)亚型组织学相关(P = 0.0002)。此外,肥大细胞数量与CD68+和CD163+巨噬细胞数量呈负相关(分别为P = 0.0001和P = 0.003),与颗粒酶+细胞毒性细胞数量也呈负相关(P = 0.004)。肥大细胞浸润程度在结节硬化亚型的cHL中并非预后因素。相比之下,在混合细胞型cHL中,大量肿瘤内肥大细胞与总体生存率(P = 0.03)和无事件生存率(P = 0.01)显著较差的结果相关。有必要进一步研究这种不良结局背后的生物学机制及其可能的治疗意义。