Expressionsmuster und prognostische Bedeutung von CD24, p53 und p21 in Lymphomen

Went, Philip; Dellas, T.; Bourgau, Caroline; Maurer, Robert; Augustin, Florian; Tzankov, Alexandar; Dirnhofer, Stephan

doi:10.1055/s-2004-831850

Cited by 12 publications

(4 citation statements)

References 16 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite CD24 being used as a differentiation marker of lymphocytes in the hematology field, only a few studies have reported on CD24 in mature B-cell lymphoma related to its expression and clinical impact. Went et al reported that CD24 was expressed in 0-20% of mature B-cell lymphoma, depending on the subtype of B-cell lymphoma, and expressed in 9% of DLBCL cases [32]. The frequency of CD24 expression in DLBCL was comparable to our IHC results.…”

Section: Discussionsupporting

confidence: 88%

CD24 is a surrogate for ‘immune‐cold’ phenotype in aggressive large B‐cell lymphoma

Higashi

Momose

Takayanagi

et al. 2022

The Journal of Pathology CR

View full text Add to dashboard Cite

The tumor microenvironment (TME) is a critical regulator of the development of malignant lymphoma. Therapeutics targeting the TME, especially immune checkpoint molecules, are changing the treatment strategy for lymphoma. However, the overall response to these therapeutics for diffuse large B‐cell lymphoma (DLBCL) is modest and new targets of immunotherapy are needed. To find critical immune checkpoint molecules for DLBCL, we explored the prognostic impact of immune checkpoint molecules and their ligands using publicly available datasets of gene expression profiles. In silico analysis of three independent datasets (GSE117556, GSE10846, and GSE181063) revealed that DLBCL expressing CD24 had a poor prognosis and had a high frequency of MYC aberrations. Moreover, gene set enrichment analysis showed that the ‘MYC‐targets‐hallmark’ (false discovery rate [FDR] = 0.024) and ‘inflammatory‐response‐hallmark’ (FDR = 0.001) were enriched in CD24‐high and CD24‐low DLBCL, respectively. In addition, the expression of cell‐specific markers of various immune cells was higher in CD24‐low DLBCL than in CD24‐high DLBCL. CIBERSORT analysis of the datasets showed fewer macrophages in CD24‐high DLBCL than in CD24‐low DLBCL. Additionally, immunohistochemical analysis of 335 cases of DLBCL showed that few TME cells were found in CD24‐high DLBCL, although statistical differences were not observed. These data indicate that CD24 expression suppresses immune cell components of the TME in DLBCL, suggesting that CD24 may be a target for cancer immunotherapy in aggressive large B‐cell lymphoma.

show abstract

Section: Discussionsupporting

confidence: 88%

CD24 is a surrogate for ‘immune‐cold’ phenotype in aggressive large B‐cell lymphoma

Higashi

Momose

Takayanagi

et al. 2022

The Journal of Pathology CR

View full text Add to dashboard Cite

show abstract

“…Some studies showed that the p53 + /p21 − (Δ p53 ) immunophenotype, used as a surrogate for p53 mutations, is associated with treatment failure and poor survival in DLBCL as well, particularly in GC DLBCL (Moller et al 1999; Pagano et al 2001; Visco et al 2006). We recently performed a TMA-based study on 297 DLBCL considering the prognostic significance Δ p53 (Went et al 2004), which was found in 21% of cases. In a multivariate model, high IPI and Δ p53 were independent prognostic markers of poor survival.…”

Section: Prognostic Significance Of Immunophenotypic Cell Cycle-and Amentioning

confidence: 99%

“…Taking into consideration these statistic operators, we critically re-evaluated our own TMA series of 301 primary DLBCL (Tzankov et al 2003a; Went et al 2004; Zinzani et al 2005; Tzankov et al 2005a; Tzankov et al 2006) to determine the optimal cut-off values for differentiation-associated antigen expression (Table 2). We linked the results to the clinical end-point “disease-related mortality” and critically compared the outcomes obtained considering the cut-off levels form the ROC curves and Y with those suggested in the literature.…”

Section: Implementation Of Receiver Operating Characteristic (Roc) Cumentioning

confidence: 99%

“…Furthermore, we reconsidered our own retrospective data on 301 primary DLBCL cases obtained on a previously validated TMA (Tzankov et al 2003a; Went et al 2004; Zinzani et al 2005; Tzankov et al 2006) in light of powerful statistical methods that determine the optimal cutoff values of phenotypic factors for efficient outcome prediction. Since DLBCL with plasma-blastic differentiation and acquired immunodeficiency syndrome-related lymphomas, as well as primary mediastinal B-cell lymphomas, are beyond the scope of our review, we refer to recent overviews on these rare variants (Carbone and Gloghini, 2005; Teruya-Feldstein, 2005; Levine, 2006; Savage, 2006).…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Prognostic Significance ofin situPhenotypic Marker Expression in Diffuse Large B-cell Lymphomas

2007

View full text Add to dashboard Cite

Diffuse large B-cell lymphomas (DLBCL) are the most common lymphoid malignancies, and encompass all malignant lymphomas characterized by large neoplastic cells and B-cell derivation. In the last decade, DLBCL has been subjected to intense clinical, phenotypic and molecular studies, and were found to represent a heterogeneous group of tumors. These studies suggested new disease subtypes and variants with distinct clinical characteristics, morphologies, immunophenotypes, genotypes or gene expression profi les, associated with distinct prognoses or unique sensitivities to particular therapy regimens. Unfortunately, the reliability and reproducibility of the molecular results remains unclear due to contradictory reports in the literature resulting from small sample sizes, referral and selection biases, and variable methodologies and cut-off levels used to determine positivity. Here, we review phenotypic studies on the prognostic signifi cance of protein expression profi les in DLBCL and reconsider our own retrospective data on 301 primary DLBCL cases obtained on a previously validated tissue microarray in light of powerful statistical methods of determining optimal cut-off values of phenotypic factors for prediction of outcome.

show abstract

Hypoxia-inducible factors in mantle cell lymphoma: implication for an activated mTORC1→HIF-1α pathway

et al. 2010

View full text Add to dashboard Cite

Aberrant activation of phosphoinositide-3 kinase/Akt (PI3K/Akt) and mammalian target of rapamycin (mTOR) signaling is implicated in the pathogenesis of mantle cell lymphoma (MCL). We previously showed oncogenic activation of PI3K/Akt pathway in a subset of MCL patients. In this study, we investigated downstream the immunohistochemical expression of (Ser2448)pmTOR [indicative of mTOR complex 1 (mTORC1) activation status] as well as of hypoxia-inducible factor 1 alpha (HIF-1α), hypoxia-inducible factor 2 alpha (HIF-2α), p53, and p21 in the same series of MCL patients. Additionally, correlation of these proteins with activated Akt ((Ser473)pAkt) and established histological prognostic factors was examined. Thirty-five tissue samples (28 classical type and seven blastoid variant) were included. The neoplastic cells expressed (Ser2448)pmTOR in 61.7%, HIF-1α in 73.5%, HIF-2α in 23.5%, and p53 in 18.2% of patients, while p21 was negative in all examined samples. In addition, 72% of patients who expressed HIF-1α had also (Ser2448)pmTOR expression (p = 0.041). HIF-1α expression was also correlated to an elevated (≥30%) Ki-67 (p = 0.031) and blastoid variant of disease (p = 0.017). In conclusion, we report for the first time common expression of HIF-alphas, especially HIF-1α, in MCL patients. Furthermore, an overall activation of mTORC1→HIF-1α axis and a potential role of (Ser2448)pmTOR in the regulation of HIF-1α in MCL patients are suggested. Finally, HIF-1α appears to be associated with more aggressive disease. A pathogenetic role for both mTORC1 and HIF-1α in MCL is implied, which will possibly lead to more efficient target therapies.

show abstract

Expressionsmuster und prognostische Bedeutung von CD24, p53 und p21 in Lymphomen

Abstract: The TMA-technology allows also in lymphoma research the simultanous, cost-effective and standardized analysis of large patient cohorts. Deltap53 revealed as an independent negative prognostic factor in diffuse large B-cell lymphomas. It can easily be determined in daily routine practice.

Cited by 12 publications

References 16 publications

CD24 is a surrogate for ‘immune‐cold’ phenotype in aggressive large B‐cell lymphoma

CD24 is a surrogate for ‘immune‐cold’ phenotype in aggressive large B‐cell lymphoma

Prognostic Significance ofin situPhenotypic Marker Expression in Diffuse Large B-cell Lymphomas

Hypoxia-inducible factors in mantle cell lymphoma: implication for an activated mTORC1→HIF-1α pathway

Contact Info

Product

Resources

About