SP 2

Validation of prognostically relevant stroma signatures in the prospectively randomized RICOVER60 and MegaCHOEP phase II and phase III trials

Diffuse large B-cell lymphoma (DLBCL) is one of the most common type of B-cell non-Hodgkin lymphoma in western countries. DLBCL represents a heterogenous malignancy with respect to clinical outcome and genetic parameters. However, until now these features are not considered in daily routine diagnostics and in clinical trials. The acquisition of underlying genetic features of DLBCL patients is often difficult in routine diagnostic samples, altough it is well-known that the occurrence of specific biological risk factors could stratify DLBCL patients in different risk groups, which might be essential for subsequent chemotherapeutic strategies.

Handling of tissue samples for routine diagnostic and genetic approaches.
Insertion of a lymph node sample in a tissue capsule (A) with subsequent formalin-fixation and paraffine-embedding for prolonged stability of the tissue sample (=FFPE-block) (B). For further investigations thin slices of the FFPE-block, prepared with a microtome (C), can be used for the measurement of gene expression (D).

Within the MMML-project the analysis of gene expression, indicating the activity of certain genes, is of pivotal interest to obtain insights into the interaction of tumor cells with their surrounding fibroblastic cells (stromal cells). Whether these measurements are significant also in patients´ tissues treated in clinical trials, is the main topic of the subproject WP2.

Investigation of the gene activity in DLBCL samples.
In addition to the tumor cells tissue samples of DLBCL patients contain non-malignant stromal cells (T-cells, follicular dendritic cells, macrophages) (A). For the subsequent gene expression analysis a profile of the gene activity is created for all cell types (B).

The main goal of the present project, therefore, is the investigation of established molecular classification systems, which have been developed within the other subprojects, with special regard to their robustness in clinical trials and their applicability in routine sample material. Validation of the obtained data in prospective, randomized patient cohorts of the German Study Group of High-Grade Lymphomas (DSHNHL) might provide information on individual patients´ prognosis, allowing for an optimized treatment of these patients.