CD40 expression identifies a prognostically favourable subgroup of diffuse large B-cell lymphoma

Abstract

In order to confirm our earlier findings of the prognostic effects of CD23 and CD40 expression in diffuse large B-cell lymphoma (DLBCL), possibly due to association with the germinal center (GC) phenotype and/or an increased autologous tumour response, tumour specimens from 125 patients with de novo DLBCL were investigated for immunohistochemical expression of CD23, CD40, BCL6, CD10, MUM1, CD4 and CD8. CD40 was positive in 64% and was associated with improved overall survival (p = 0.03). A GC phenotype was present in 47%, and was also associated with a better overall survival (p = 0.006) but did not correlate with CD40-expression. There was no correlation between amount of tumour infiltrating T-cells and CD40-positivity. CD23 was positive in 10% and expression did not correlate with prognosis. In conclusion, the prognostic effect of CD40 expression was confirmed, but did not correlate with GC-phenotype or T-cell infiltration.

CD40 is a potential marker of favorable prognosis in patients with diffuse large B-cell lymphoma treated with immunochemotherapy

“…Our results demonstrate a potential prognostic advantage of CD40 expression even after the incorporation of rituximab to lymphoma therapies. The finding is in accordance with our previous observations regarding the prognostic importance of CD40 in DLBCL [3,4] using a cut-off level of 10%, although in the present series, this was not independent of IPI category.…”

“…Trials with CD40 agonists in B-cell malignancies and solid tumors have shown promising results [16]. A possible mechanism is increased antigen presentation followed by enhanced T-cell response directed against tumor antigens [17], although we observed no correlation between CD40-positivity and high amount of tumor infiltrating T-cells in DLBCL in an earlier study [4].…”

“…We have previously demonstrated and confirmed that immunohistochemically defined expression of CD40 in DLBCL results in a favorable prognosis [3,4]. In those studies, the patients were treated with anthracycline-based chemotherapy without rituximab.…”

Genes associated with the tumour microenvironment are differentially expressed in cured versus primary chemotherapy‐refractory diffuse large B‐cell lymphoma

“…Three 0AE6 mm-diameter core biopsies were punched out from the representative areas of each paraffin block and positioned in a recipient paraffin block using a custom-made precision instrument. As TMA might be less reliable for evaluating degree of infiltrating T-cells (Linderoth et al, 2007), OTS was also used when available.…”

Quantitative Assessment and Classification of Tissue-Based Biomarker Expression With Color Content Analysis

“…[3][4][5][6][7][8] Other biomarkers that are being investigated include p53 9,10 and Ki-67 11,12 for breast cancer, Bcl-2 for melanoma, 13 the epidermal growth factor receptor for lung cancer, 14 apoptotic protease activating factor-1 15 for colorectal cancer, and CD23 and CD40 for lymphoma. 16 The most commonly used technique to evaluate tissue-based biomarkers is immunohistochemistry (IHC), owing to its relatively low cost and increased time efficiency over other methods, such as ligand-binding assays 17,18 or fluorescence in situ hybridization. 19 Immunohistochemistry assessment is typically performed by pathologists using optical microscopy, although digital microscopy is increasingly, albeit slowly, being adopted in practice, [20][21][22] following the path of radiology.…”