Tumor-infiltrating macrophages correlate with adverse prognosis and Epstein-Barr virus status in classical Hodgkin's lymphoma

Abstract

BackgroundClassical Hodgkin's lymphoma is characterized by a minority of neoplastic cells surrounded by a heterogeneous background population of non-neoplastic cells including lymphoma-associated macrophages. High levels of expression of both the monocyte/macrophage lineage-associated antigens CD68 and CD163 have been suggested to have pro-tumor effects. The aim of our study was to correlate expression of CD68 and CD163 with the clinico-pathological features and prognosis of a cohort of patients with previously untreated Hodgkin's lymphoma. Design and MethodsA tissue microarray was constructed from paraffin-embedded tumor tissues from 288 cases of classical Hodgkin's lymphoma. CD68 and CD163 expression was assessed immunohistochemically and the degree of macrophage infiltration within the tumor was scored using point grid counting. Clinical data were obtained from clinical records. ResultsThe patients' median age was 37 years (range, 6-86 years). The male to female ratio was 1.2. In classical Hodgkin's lymphoma (n = 288) high CD68 and CD163 expression correlated, at the univariate level, with poorer overall survival (P=0.002 and P=0.03, respectively) and event-free survival (P=0.03 and P=0.04, respectively). At the multivariate level, high CD68 expression remained significantly predictive of overall survival (P=0.004). In addition, we demonstrated that both high CD68 and CD163 expression were associated with the presence of Epstein-Barr virus in the neoplastic cells (P=0.001 and P=0.0002, respectively). ConclusionsIn classical Hodgkin's lymphoma, high expression of the macrophage/monocyte-related antigens CD68 and CD163 correlates with adverse outcome and with the presence of Epstein-Barr virus in the tumor cell population.

Spindle-shaped CD163+ rosetting macrophages replace CD4+ T-cells in HIV-related classical Hodgkin lymphoma

“…[10][11][12] However, other studies could not confirm this finding. 13,14 In the present study, we aimed to further characterize the morphologic and immunohistochemical characteristics of HIV-associated Hodgkin lymphoma in comparison to classical Hodgkin lymphoma in non-HIV infected individuals with respect to the composition of the microenvironment and the tumor cell content.…”

“…A high number of macrophages has been correlated with frequent treatment failure in classical Hodgkin lymphoma. [10][11][12] As the cases in the present series were collected over a long period of time, treatment protocols were heterogeneous and clinical data were not available in all cases. Therefore, the prognostic impact of macrophages in HIV-associated Hodgkin lymphoma should be assessed in future studies.…”

The Ratio of the Absolute Lymphocyte Count to the Absolute Monocyte Count Is Associated with Prognosis in Hodgkin's Lymphoma: Correlation with Tumor-Associated Macrophages

“…Pathologically, cHL is characterized by the presence of a small number of diagnostic Reed-Sternberg cells in a background of bystander reactive cells composed of lym-vestigators, including the present authors, validated the adverse prognostic impact of a high TAM content using immunohistochemical staining for CD68 and CD163 [5][6][7][8][9][10]. TAMs are believed to provide trophic factors that directly accelerate the growth and survival of malignant lymphocytes [11][12][13][14].…”

High tumour-associated macrophages infiltration is correlated with poor survival outcome in classical Hodgkin’s lymphoma

“…[16,[37][38][39][40] Also high CD68 was not found to be independent predictor of primary treatment outcome. However, different studies reported different association of high CD68 with some clinicopathological findings as B symptoms, [38,41,42] age, [35,41] mixed cellularity subtype, [5,35,[41][42][43] primary treatment failure, [5,19,36,38] male sex, [35] bulky disease, [35] and IPS. [35,37,41] In our study, there was association between high CD68+ TAM infiltration and higher disease stage similar to previous reports.…”

“…However, different studies reported different association of high CD68 with some clinicopathological findings as B symptoms, [38,41,42] age, [35,41] mixed cellularity subtype, [5,35,[41][42][43] primary treatment failure, [5,19,36,38] male sex, [35] bulky disease, [35] and IPS. [35,37,41] In our study, there was association between high CD68+ TAM infiltration and higher disease stage similar to previous reports. [19,35,42,44] In the present study, we demonstrated a positive correlation between high CD68+ TAM infiltration and shortened DFS but not DSS.…”