Building an Outcome Predictor Model for Diffuse Large B-Cell Lymphoma

Abstract

Diffuse large B-cell lymphoma (DLBCL) patients are treated using relatively homogeneous protocols, irrespective of their biological and clinical variability. Here we have developed a protein-expression-based outcome predictor for DLBCL. Using tissue microarrays (TMAs), we have analyzed the expression of 52 selected molecules in a series of 152 DLBCLs. The study yielded relevant information concerning key biological aspects of this tumor, such as cell-cycle control and apoptosis. A biological predictor was built with a training group of 103 patients, and was validated with a blind set of 49 patients. The predictive model with 8 markers can identify the probability of failure for a given patient with 78% accuracy. After stratifying patients according to the predicted response under the logistic model, 92.3% patients below the 25 percentile were accurately predicted by this biological score as "failure-free" while 96.2% of those above the 75 percentile were correctly predicted as belonging to the "fatal or refractory disease" group. Combining this biological score and the International Prognostic Index (IPI) improves the capacity for predicting failure and survival. This predictor was then validated in the independent group. The protein-expression-based score complements the information obtained from the use of the IPI, allowing patients to be assigned to different risk categories.

PKC-beta II expression has prognostic impact in nodal diffuse large B-cell lymphoma

“…Among the 186 cases tested, 30% were positive, but PKC beta II expression had no impact in the failure-free survival. 9 However, primary extranodal lymphomas were included in their analysis.…”

“…Cases were considered positive if the antibody expression was detected in 410% of the lymphoma cells. 9 Reactive tonsils were used as external positive controls. The PKC-beta II antibody stained normal plasma cells and mantle zone lymphocytes strongly.…”

“…3,4 Two studies have recently analyzed the prognostic impact of PKC-beta II expression by immunohistochemistry in patients with DLBCL, with conflicting results. 8,9 While Hans et al 8 verified that the expression of PKC-beta II imparted a bad prognosis to the patients, the study by Sáez et al 9 found no association between PKC-beta II expression and clinical outcome in these patients.…”

Nuclear bcl10 expression characterizes a group of ocular adnexa MALT lymphomas with shorter failure-free survival

“…[17][18][19][20] The use of tissue microarrays could be particularly useful in this context, since tumoral specimens in ocular adnexa lymphomas are frequently small, fully embedded in paraffin, and require microdissection or tissue-core selection to guarantee that the analysis reports on the features of the tumoral cells.…”

“…In order to elucidate the biology of ocular adnexa MALT lymphomas we have analyzed a tissue microarray including a large series of 39 cases with a panel of antibodies and probes directed against molecules known to be involved in B-cell differentiation, cell cycle and apoptosis control, [17][18][19][20] and, for control purposes, compared them with some non-MALT lymphomas from the same anatomical region. Moreover, we have included in the analysis a tissue-microarray in situ hybridization study of the apoptotic index (TdT-mediated biotin-dUTP nickedend labeling (TUNEL)), and of t(11;18)(q21;q21) and t(14;18)(q32;q21), which are characteristic translocations of MALT lymphomas.…”