Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome

Greaves, Paul; Clear, Andrew; Coutinho, Rita; Wilson, Andrew; Matthews, Janet; Owen, Andrew; Shanyinde, Milensu; Lister, T. A.; Calaminici, Maria; Gribben, John G.

doi:10.1200/jco.2011.39.9881

Cited by 137 publications

(138 citation statements)

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“…[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. Several studies (see Table 3) reported association of high CD68+ TAM infiltration with poor survival outcome using DFS, DSS, or overall survival (OS).…”

Section: Discussionsupporting

confidence: 64%

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: 64%

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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“…Using 1,700 cells/mm 3 as a cut-off point, patients with high nonfollicular CD20 expression had overall survival improved (p=0.003) at 5 years (87% versus 70%), at 10 years (84% versus 52%) and at 20 years (76% versus 43%). 2 Tzankov et al, in a study with 119 patients with classical HL followed for 12 years demonstrated that immunopheno- type CD30+/CD15±/CD20+ is associated with a favorable clinical outcome and CD20 was an independent positive prognostic factor (p=0.035). Failure-free survival was higher in CD20+ patients (286 months versus 202 months; p=0.022).…”

Section: Anti-cd20 Therapymentioning

confidence: 99%

“…In addition to these malignant cells, HL infiltrates comprise T cells, neutrophils, eosinophils, macrophages, fibroblast, plasma cells and mast cells. 1,2 The malignant cells are referred to as giant cells, also denominated Hodgkin Reed-Sternberg (HRS) cells, and their origin remains controversial. 1 Some theories point to either a fusion of B and non-B cells or mutation in germinal-center cells and loss of B cell receptor expression.…”

Section: Overviewmentioning

confidence: 99%

“…Macrophages may play a role in tumor support. 2 In all classical HL, tumor cells correlation with EpsteinBarr virus (EBV) infection occurs in about 20 to 40% of cases, but its role in pathophysiology is poorly understood. [4][5][6] Immunohistochemistry and gene expression profiling suggest that EBV influences the B-cell microenvironment.…”

Section: Overviewmentioning

confidence: 99%

“…[4][5][6] Immunohistochemistry and gene expression profiling suggest that EBV influences the B-cell microenvironment. 2 The classical presentation of HL is painless lymphadenopathy, usually cervical and/or supraclavicular. B symptoms as fever, unintentional loss of more than 10% of bodyweight over 6 months and fatigue are present in 25% of patients and have prognostic value.…”

Section: Overviewmentioning

confidence: 99%

See 2 more Smart Citations

CD20 role in pathophysiology of Hodgkin’s disease

Santos

Lima

2017

Rev. Assoc. Med. Bras.

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Hodgkin's lymphoma (HL) is a tumor comprising non-malignant and malignant B-cells. Classical HL expresses CD15+ and CD30+ antigens, and 20 to 40% of patients are CD20+. This antigen is a ligand free protein present in B lymphocyte cells and its function is not well known. Some studies suggest that expression of CD20 may play a major role in Hodgkin's disease pathophysiology and may affect the patients' treatment prognosis, as well as relapse and refractory response. In the past few years, development of monoclonal anti-CD20 antibodies changed drastically the treatment for non-Hodgkin lymphomas in which CD20 is expressed. HL treatment is essentially composed of radiotherapy and chemotherapy; however, monoclonal anti-CD20 antibodies applicability is not well delimitated due to lack of information about clinical outcomes with anti-CD20 monotherapy or combined drug therapy using a classic regimen, as well as about CD20 pathophysiology mechanisms in B-cells tumors. The objective of our review is to discuss CD20 function in Hodgkin's lymphoma development, its influence on disease evolution and outcomes, as well as its effects on therapeutics and patients' prognostic.

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Primary refractory Hodgkin lymphoma: Limited options and poor survival—but not always

et al. 2014

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Our patient is a 32-year-old woman of Cape Verdean descent, who initially presented in February of 2010 with 1-month course of non-productive cough. She also stated that she had a few swollen lymph nodes on the right side of her neck for the past 6 months, which were initially sore, but never painful. She endorsed drenching night sweats and a 20-pound weight loss over the last 6 months, but denied any fever or chills. Her past medical history and family history were non-contributory. She is a cigarette smoker with a 10 pack-year history of cumulative smoking. After a course of antibiotics that had no effect on her lymphadenopathy, she had a cervical lymph node excisional biopsy. Am. J. Hematol. 89:853-857, 2014. V C 2014 Wiley Periodicals, Inc.The differential diagnosis on this young woman with lymphadenopathy is broad and includes autoimmune such as systemic lupus erythematosus, chronic infections such as tuberculosis, and oncological processes. Given the presence of B symptoms, namely night sweats and 20-pound weight loss, I would favor an oncological condition such as lymphoma. The clinical picture is highly suspicious for Hodgkin lymphoma (HL), which has been associated with cigarette smoking based on a recent meta-analysis of epidemiological studies [1]. The differential diagnosis also includes follicular lymphoma (FL) and head and neck (H&N) cancer. FL, however, tends to present in older patients with B symptoms reported in only 20-30% of the cases. H&N cancer also tends to present in older individuals and has a strong male predominance. Given the 6-month clinical course, I would not favor more aggressive disorders such as Burkitt or diffuse large B-cell lymphoma.The hematoxylin and eosin sections demonstrated a polymorphic lymphoid population focally intersected by broad areas of fibrosis. The lymphoid infiltrate consists of small-to-medium-sized lymphocytes with a background of scattered eosinophils, histiocytes, and neutrophils. Occasional large binucleated hyperchromatic cells with prominent nucleoli (Reed-Sternberg cells) are noted within this infiltrate. Per immunohistochemistry, the Reed-Sternberg cells are positive for expression of CD30 and CD15, and negative for CD3, CD20, ALK-1, granzyme B, cytomegalovirus (CMV), Epstein-Barr virus, and herpes simplex virus. These findings are diagnostic of classical HL, nodular sclerosing (NS) variant.Not surprisingly, we have a pathological diagnosis of classical HL, NS variant. Although included in the group of classical HL, the NS variant is the most common, accounting for approximately 60% of the cases. The NS variant seems to be associated with a better prognosis than other variants such as mixed cellularity (MC) and lymphocyte-depleted (LD) HL. Based on a recent population-based study from the SEER database, patients with NS had higher relative survival and lower lymphoma-related death rates at 5 years than patients with MC or LD HL [2]. To complete this patient's staging and prognostic workup, a positron emission tomography/computed tomography (PET/CT) s...

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Expression of FOXP3, CD68, and CD20 at Diagnosis in the Microenvironment of Classical Hodgkin Lymphoma Is Predictive of Outcome

Cited by 137 publications

References 32 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

CD20 role in pathophysiology of Hodgkin’s disease

Primary refractory Hodgkin lymphoma: Limited options and poor survival—but not always

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