The prognostic relevance of tumor associated macrophages in advanced stage classical Hodgkin lymphoma

Jaković, Ljubomir; Mihaljević, Biljana; Jovanović, Maja; Bogdanović, Andrija; Andjelic, Bosko; Bumbaširević, Vladimir

doi:10.3109/10428194.2011.580026

Cited by 52 publications

(45 citation statements)

References 42 publications

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“…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.…”

Section: Discussionsupporting

confidence: 81%

“…Similar findings were reported in previous studies. [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.…”

Section: Discussionmentioning

confidence: 96%

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

Al-Maghrabi

Gomaa

Al-Mansouri

et al. 2015

JST

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Background: Classical Hodgkin's lymphoma (cHL) represents the majority of HLs with a relatively good prognosis. In 20% of patients, primary treatment fails. Prediction of treatment failure is critical. A gene signature of tumour associated macrophages (TAM) correlated with response to treatment as CD68 positive TAM was found to be associated with shortened survival. We aim to investigate the relation CD68+TAM infiltration to patients' outcome. Patients and Methods: Pathological materials of 115 patients with cHL were used. Clinical characteristics of patients were collected from the records. CD68 immunostaining was performed to determine the number of infiltrating TAM and subsequently followed by stratification of results. Results of CD68 immunostaining were statistically analysed to correlate the extent of CD68+ TAM infiltration with clinicopathological characteristics, treatment outcome, and patients' survival. Results: High CD68+TAM infiltration was observed in more patients of cHL (96/115 of patients = 83.5%). High CD68+TAM infiltration was associated with extranodal presentation (P = .001), and higher stage (P = .022). No associations with other clinicopathological parameters were found. High CD68+TAM infiltration was not found to be an independent predictor of treatment outcome. High CD68+TAM infiltration correlated with disease free survival (DFS) (log-rank = 4.505, P = .034) but not with disease specific survival (DSS) (log-rank = 1.371, P = .242). Conclusions:The results of our study support the adverse prognostic effect of high TAM in cHL. Technical standardisation of CD68 immunostaining is required to establish TAM infiltration as a prognostic predictor. Also in vivo and in vitro cHL models have to be established for proper understanding of the role of CD68 in modulating the TAM in cHL.

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Section: Discussionsupporting

confidence: 81%

Section: Discussionmentioning

confidence: 96%

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

Al-Maghrabi

Gomaa

Al-Mansouri

et al. 2015

JST

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“…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].…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2012

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Background. Although most patients with classical Hodgkin's lymphoma (cHL) have a long survival duration, the current risk stratification is imperfect. A recent study suggested a prognostic role for the peripheral blood absolute lymphocyte count/absolute monocyte count (ALC/AMC) ratio at diagnosis in cHL. It is intriguing to investigate the significance of the ALC/AMC ratio in relation to tumor-associated macrophages (TAMs), yet another prognostic factor for cHL.Methods. We examined the prognostic impact of the ALC, AMC, and ALC/AMC ratio in 312 cHL patients (median age, 37 years) using receiver operating characteristic curve analysis for optimal cutoff values, and compared these with TAM content.Results. The median follow-up was 65 months (range, 0.1-245 months). On univariate analysis, a low ALC/AMC

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“…69,70 Indeed, overexpression of macrophage antigens in tumor tissue may indicate a prometastatic state and may be associated with poor prognosis. 71,72 The molecular mechanisms leading to the expression of immune antigens by tumor cells remain still incompletely understood. The intercellular genetic exchange through cell fusion or release of exosomes may have a role in induction of immune markers in cancer cells.…”

Section: Cd68 In Cancermentioning

confidence: 99%

CD68/macrosialin: not just a histochemical marker

Chistiakov

Killingsworth

Myasoedova

et al. 2017

Laboratory Investigation

523

330

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CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.

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The prognostic relevance of tumor associated macrophages in advanced stage classical Hodgkin lymphoma

Cited by 52 publications

References 42 publications

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

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

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

CD68/macrosialin: not just a histochemical marker

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