Immunohistochemical Analysis of the Expression of the B- Cell Markers BCL-6, MUM1/IRF4, CD79A and Transcription Factors BOB.1 and OCT.2 in Classical Hodgkin Lymphoma.

INTRODUCTION: Classical hodgkin’s lymphoma can be considered in most cases as a B-cell lymphoma by the presence of potentially functional immunoglobulin gene rearrangements in Hodgkin/Reed Sternberg (H-RS) cells However the expression of B cell markers in classical Hodgkin lymphoma is rare and the light and heavy chain mRNA is lacking. The exact mechanism for this discrepancy is not known, and some studies have suggested a transcription machinery deficiency.

The aim of our study was the detection of B cell markers like CD79a, bcl6 and MUM.1/IRF4 in relation to B cell transcription factors BOB.1 and OCT.2 in classical Hodgkin lymphoma in order to define subgroups with different histogenesis and prognosis.

Patients and methods: The analysis included 107 cases of classical Hodgkin lymphoma 55 males and 52 females with a median age of 37 (13–79). They were staged as: 17 stage I, 55 stage II, 13 stage III and 22 stage IV. Advanced stage patients were risk stratified according to the IPI, and early according to EORTC. The histological subtype was: Nodular sclerosis 76, Mixed cellularity 19, Lymphocyte depleted 5 and lymphocyte rich 7 cases. Extranodal disease was present in 24/107 (22.4%) cases. Diagnostic biopsies were used for histochemical detection of bcl/6, CD79a, MUM-IRF4 and B cell transcription factors BOB.1, OCT.2. Expression was considered as low if detected in 1–25%, medium in 26–49% and high in > 50% of H/RS cells.

RESULTS Bcl6 was expressed in 22/101 cases, MUM.1 in 81/107 cases, BOB.1 in 89/100, OCT.2 in 17/100 and CD79a in 6/101 cases. In positive cases, bcl6, CD79a and OCT.2 have shown low expression, while MUM.1 and BOB.1 had a high expression in the majority of cases. There was not any difference in the expression pattern between different histologic subtypes for all these markers. Bcl6, MUM.1, OCT.2 and CD79a expression were not significantly different for different risk group categories and did not influence overall survival, disease free survival or time to progression. Cases positive for MUM expression had a significantly lower Hb (p=0.03), lower albumin (p=0.02), and higher IgG value (p=0.01). BOB.1 was expressed in 25% of early favourable, in 35% of intermediate and 40% of unfavourable early stage disease (p=0.06).There was a positive correlation between B symptoms and BOB.1 expression (p=0.01). There was a positive correlation between the expression of bcl6 and OCT.2 and between OCT.2 and CD79a (p=0.05, p=0.01) respectively.

CONCLUSION MUM is expressed in the majority of classical Hodgkin lymphoma cases confirming its histogenesis from a late centrocyte and post/germinal centre B cell. B cell markers and transcription factors were not significant for survival, disease free survival and time to progression and their expression pattern was not different between different histological subtypes and risk groups of classical Hodgkin lymphoma.