Publication details
VALIDATION OF SELECTED PROTEIN KINASE C ISOPHORMS FOR DIFFUSE LARGE B-CELL LYMPHOMA OUTCOME PREDICTION
| Authors | |
|---|---|
| Year of publication | 2005 |
| Type | Article in Periodical |
| Magazine / Source | Annals of Oncology |
| MU Faculty or unit | |
| Citation | |
| Field | Oncology and hematology |
| Keywords | Lymphoma; protein kinase C; prediction |
| Description | Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkins lymphoma, characterized by its clinical heterogenity. Global gene expression profiling subdivide the DLBCL into two main clinically and biologically distinct subgroups. Gene expression signatures characteristic of particular subgroups include different isophorms of protein kinase C (PKCs). According microarrays analyses, the increased expression of PKC-delta (PKCD) and PKC-gamma (PKCG) is present in DLBCL with favourable prognosis, but PKC beta I (PKCBI) and II (PKCBII) is present in fatal or refractory DLBCL. Methods: We used Reverse-Transcription PCR (RT-PCR), Quantitative Real-Time PCR (QRT-PCR) and immunohistochemical (IHC) analyses to validate the expression of selected PKCs isophorms in formalin fixed and paraffin embed (FFPE) tumor specimens from 52 patients treated for DLBCL between 1996 and 2003. Results: 1) We developed modified technique for RNA isolation from FFPE tumor specimens producing RNA of sufficient quantity and suitable quality for RT-PCR and QRT-PCR. 2) Using the IHC, RT-PCR, QRTPCR and DNA sequenation we confirmed that B-lymphocytes do not express PKCG. 3) We found that DLBCL patients, who achieved complete or partial remission after the first course of chemotherapy, and patients remained alive at 20-month follow-up, express low level of PKCD mRNA (P = 0.0089 and P = 0.0064 respectively). Conclusions: Data from microarray analyses need to be interpreted cautiously. PKCD seems to be potential predictive and prognostic marker in DLBCL. |