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

Abstract

Although the treatment of Hodgkin lymphoma (HL) has been improved, distinguishing reliable prognostic biomarkers could better stratify patients for more effective treatment. We analyzed the prognostic relevance of CD68+ tumor-associated macrophages (TAMs) by immunohistochemical analysis at diagnosis and standard clinical parameters in 52 ABVD (doxorubicin, bleomycin, vinblastine, dacarbazine)-treated patients with advanced stage classical HL (cHL). Patients with >25% CD68+ TAMs compared to those with ≤25% had worse 5-year overall survival (45% vs. 77%, log-rank p = 0.019) and showed a trend toward shorter 5-year event-free survival (51% vs. 71%, log-rank p = 0.19). Additionally, no significant correlation with selected clinical features was found. Significantly shorter 5-year overall survival was associated with International Prognostic Score (IPS) >2, bulky disease, elevated erythrocyte sedimentation rate (log-rank test, p = 0.003, p = 0.049, p = 0.007, respectively). In multivariate analysis, increased CD68+TAMs, IPS >2, and bulky disease were identified as independent prognostic factors for overall survival (Cox multivariate model, p = 0.006, p = 0.007, p = 0.013, respectively). Tumor-associated macrophages represent a potential prognostic biomarker which could contribute to better risk stratification of patients with cHL.

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

“…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.…”

“…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.…”

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].…”

CD68/macrosialin: not just a histochemical marker

“…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.…”