CD68-positive tumor-associated macrophages predict unfavorable treatment outcomes in classical Hodgkin lymphoma in correlation with interim fluorodeoxyglucose-positron emission tomography assessment

Abstract

Finding new prognostic factors to identify patients with Hodgkin lymphoma (HL) at risk of treatment resistance or relapse remains challenging in daily practice. We evaluated the relationship between CD68 expression, interim positron emission tomography (iPET) results and outcome in 158 patients with HL diagnosed from February 1995 to July 2011. Immunohistochemistry (anti-CD68) gave two groups: low with ≤25% positive cells (121 patients) and high with >25% (37 patients). Five-year overall survival was higher in the low group (88.4% vs. 63.2%, p=0.0151), as was progression-free survival (74.5% vs. 40.7%, p=0.0003). In 68 patients evaluable, iPET correlated with CD68: 13/52 patients (25%) in the low group had positive iPET as compared to 11/16 patients (68%) in the high group (p=0.0016). This study confirms the prognostic value of CD68 in HL. We found a correlation between CD68 and iPET suggesting potential for a better stratification.

Absolute Monocyte Count and Lymphocyte-Monocyte Ratio Predict Outcome in Nodular Sclerosis Hodgkin Lymphoma: Evaluation Based on Data From 1450 Patients

“…29 It seems most appropriate that combined analysis of the total PET-CT uptake and quantitation of the AMC in patients with cHL will serve as a combination of valuable surrogate markers for detecting disease activity. It is of interest to note that Touati et al 10 have recently reported pioneering studies demonstrating that increases in CD68-positive TAMs predict an unfavorable outcome in cHL, when correlated with interim fluorodeoxyglucose-positron emission tomography (PET) assessment. In this respect, analysis regarding the role of AMC in combination with PET-CT data has already been reported to be considerable in NHL.…”

“…[2][3][4][5][6][7] The rationale for using AMC as a prognostic parameter in cHL is even more relevant than in other malignancies because of the immunohistochemical and molecular data, including gene expression profile, which identify a key role for monocytes and macrophages in the biology of cHL, particularly in patients with nodular sclerosis (NS) histology. [8][9][10][11][12] Combining AMC and ALC as a lymphocytemonocyte ratio (LMR) has been proposed and shown to have prognostic potential in both non-Hodgkin lymphoma (NHL) and cHL. 13,14 Each of the above studies has used different cutoff values for AMC and LMR, which are easily accessible and simple to apply, but an agreed standard value has as yet not been defined.…”

Immunologic pathomechanism of Hodgkin's lymphoma

“…Angiogenesis is controlled through vascular endothelial growth factor along with endothelial and smooth muscle cells. The unfavorable prognostic role of CD68 þ macrophages has been reported previously [58][59][60]. Tumor-infiltrating CD68 þ macrophages can help to distinguish patients with a high risk for early relapse and those who are overtreated despite of their good prognosis.…”

Tumor-associated macrophages predict inferior outcomes in classic Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial

“…5 Steidl et al showed a macrophage gene expression signature to be associated with primary treatment failure in CHL and subsequently showed, using an independent validation cohort, that increased CD68 IHC expression was associated with inferior outcomes, including outcome after salvage treatment with autologous stem cell transplantation. 6 Since then, most, [7][8][9][10][11][12][13][14][15][16][17][18] but not all, 12,[18][19][20] subsequent studies have confirmed the inferior prognostic significance of TAMs in CHL using CD68 and/or CD163 IHC. In addition, early interim positron emission tomography analysis after 2 courses of chemotherapy has prognostic value in advanced-stage CHL, and increased CD68 IHC expression was recently shown to be associated with a higher rate of early positron emission tomography positivity.…”

“…In addition, early interim positron emission tomography analysis after 2 courses of chemotherapy has prognostic value in advanced-stage CHL, and increased CD68 IHC expression was recently shown to be associated with a higher rate of early positron emission tomography positivity. 8 However, there has been variability in suggested threshold values for CD68 and CD163 IHC expression in the literature. This variability may reflect differences in IHC quantitation methodology between studies, the use of manual visual scoring techniques, and lack of subsequent validation of thresholds in their respective studies.…”