Tumor-associated macrophages predict inferior outcomes in classical Hodgkin lymphoma: a correlative study from the E2496 Intergroup trial
Menée initialement sur une cohorte de 143 patients atteints d'un lymphome hodgkinien classique, puis validée sur une cohorte de 144 patients supplémentaires, cette étude évalue l'association entre des marqueurs des macrophages associés aux tumeurs et le pronostic de la maladie
Increased tumor-associated macrophages (TAMs) are reported to be associated with poor prognosis in classical Hodgkin lymphoma (CHL). We investigated the prognostic significance of TAMs in the E2496 Intergroup trial, a multicentre phase III randomized controlled trial comparing ABVD and Stanford V chemotherapy in locally extensive and advanced stage CHL. Tissue microarrays were constructed from formalin-fixed, paraffin-embedded tumor tissue and included 287 patients. Patients were randomly assigned into training (n=143) and validation (n=144) cohorts. Immunohistochemistry (IHC) for CD68 and CD163, and in-situ hybridization for EBV-encoded RNA (EBER) were performed. CD68 and CD163 IHC were analyzed by computer image analysis; optimum thresholds for overall survival (OS) were determined in the training cohort, and tested in the independent validation cohort. Increased CD68 and CD163 expression were significantly associated with inferior failure free survival (FFS) and OS in the validation cohort. Increased CD68 and CD163 expression were associated with increased age, EBER positivity and mixed cellularity subtype of CHL. Multivariate analysis in the validation cohort showed increased CD68 or CD163 expression to be significant independent predictors of inferior FFS and OS. We demonstrate the prognostic significance of TAMs in locally extensive and advanced stage CHL in a multicentre phase III randomized controlled clinical trial.
Blood , résumé, 2012