Introduction

In humans, diffuse large B-cell lymphomas (DLBCL) can be subdivided into germinal center B-cell-like (GCB) and activated B-cell-like (ABC) lymphomas based on gene expression profiles. The Choi algorithm is based on the immunohistochemical expression of GCET1, CD10, MUM1, BCL-6, and FOXP-1 to diagnose these two phenotypes. Clinically, GCBs have longer survival times compared to ABCs when treated with CHOP (cyclophosphamide, hydroxydaunorubicin, vincristine, prednisone/prednisolone) chemotherapy. No similar subclassification of DLBCLs has been established in dogs; however, variability in response to CHOP chemotherapy is commonly observed.

Objective

The goal of this study was to use matrix-assisted laser desorption/ionization (MALDI) combined with time-of-flight (TOF) mass spectrometry and a modified Choi algorithm to predict the response of canine DLBCLs to CHOP therapy and to identify similar subtypes of DLBCL as in humans.

Methods

In a case-controlled study of 10 dogs with CHOP-resistant DLBCLs and 10 dogs with CHOP-sensitive DLBCLs, sections of formalin-fixed paraffin-embedded (FFPE) neoplastic tissue were immunohistochemically labeled with antibodies against GCET1, CD10, BCL-6, BCL-2, MUM1, and FOXP1. Homogenates from FFPE tissues were also analyzed using MALDI-TOF.

Results

Using MALDI-TOF, consistent spectra were obtained from both technical and biological replicates. We identified 64% of chemosensitive and 78% of chemoresistant canine DLBCL using MALDI-TOF, and results were similar when using a slight modification of the Choi algorithm.

Conclusions

Our results indicate that MALDI-TOF and immunohistochemistry using a modified Choi algorithm may be able to predict response to chemotherapy in canine patients with DLBCL.