The role of CD68+ macrophage in classical Hodgkin lymphoma patients from Egypt

Abstract

Background: CD68+ tumor-associated macrophages (TAM) play an important role in the progression of classical Hodgkin lymphoma (cHL). We assessed the role of CD20 and CD68 + TAM in a cohort of cHL patients from Egypt and correlated the number of CD68 + cells with patients' characteristics, response to treatment, overall and progression free survival rates (OS & PFS). Methods: CD20 expression and CD68 + TAM numbers were assessed in representative tumor tissues obtained from 81 cHL patients using flowcytometry (FCM), immunohistochemistry (IHC), and Rt-PCR techniques. Results: The expression levels of CD68 protein by IHC was high in 27 (33.3%), moderate in 15 (18.5%), low in 15 (18.5%), and negative in 24 (29.6%) patients (p = 0.13). CD68-mRNA expression was high in 43/81(53.1%), and low in 38(46.9%) patients (p = 0.6). The number of CD68 + TAM (by FCM) was low (< 20 cells) in 42/81 (51.9%), and high (≥20 cells) in 39/81 (48.1%) patients (p = 0.74). CD68 expression (by FCM, IHC& Rt-PCR) associated significantly with poor response to treatment, decreased CD20 expression, reduced OS and PFS rates (p < 0.001 for all). CD68 expression (by Rt-PCR only) associated significantly with advanced disease stage (p = 0.04). The age of the patients, high CD20 expression & high CD68+ macrophage number were independent prognostic factors for OS (p= 0.02, p = 0.008 & p = 0.009; respectively). However, the age of the patient, high CD20, and high CD68+ macrophage expression (by FCM&IHC) were independent prognostic factors for DFS (p. = 0.004, p. = 0.01, p. = 0.007 and p. = 0.01; respectively). Conclusion: CD68 + TAM expression (by Rt-PCR, FCM and/or IHC) can identify patients with poor response to treatment and reduced survival rates (OS& PFS). Assessment of CD68 + positive macrophages by FCM is superior to other methods (Rt-PCR and IHC) as a prognostic factor for DFS and OS rates.

The Role of Tumor-Associated Macrophages in Hematologic Malignancies

“…These macrophages could be considered as “bad guys”, with a pro-tumor activity and a possible inhibition of drug-mediated cell death, leading to a reduced treatment response, disease progression and reduced survival [ 115 ]. Since then, many subsequent reports were published, but showed conflicting results about a definitive association between TAM and survival, as illustrated in Table 1 [ 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ].…”

“…Azambuja and colleagues showed a lack of IHC reproducibility compared to GEP, while other reports suggested CD163 could represent a more appropriate marker to detect TAM infiltration compared to CD68, that could stain myelomonocytic cells, fibroblasts and endothelial cells [ 115 , 116 , 117 , 118 , 119 , 120 , 121 , 122 , 123 , 124 , 125 , 126 , 127 , 128 , 129 , 130 ].…”

The circuitry of the tumor microenvironment in adult and pediatric Hodgkin lymphoma: cellular composition, cytokine profile, EBV, and exosomes

“…Subsequently, many studies have confirmed the association of TAMs with poor prognosis of adult HL patients (Table 1). 21‐24 A couple of studies investigated the impact of TAMs on prognosis of pediatric patients. In contrast to adult HL patients, TAMs failed to predict disease outcome in pediatric patients 8,25,26 .…”

Prognostic significance of CD163- and CD68-expressing macrophages in nodular sclerosis Hodgkin lymphoma

“…Повышение доли клеток, экспрессирующих CD163, коррелирует с вероятностью развития рецидивов заболевания и низкой общей вы живаемостью пациентов, что частично совпадает с ре зультатами зарубежных исследований, которые носят преимущественно описательный характер [9,[14][15][16]. Значимость CD68 как маркерапредиктора течения кЛХ в настоящее время доказана не в полной мере, хотя встречаются отдельные работы, в которых отра жена важная роль данного маркера [16,17].…”