CHD is a B-cell neoplasm in nearly all instances derived from the GC B cells harbouring somatically mutated IgV region genes. However, these cells have consistently lost their Ig gene transcription ability, due to functional defects in the Ig gene regulatory elements [10
]. The defect has been attributed to crippling mutations [11
], a defect in the transcription machinery due to lack of expression of the octamer transcription factor Oct2 and/or its coactivator Bob-1 [12
], or epigenetic silencing in the inhibition of IgH transcription [15
The expression of Bob-1 in H/RS cells was a surprising finding. To our knowledge, this is the first study reporting strong nuclear Bob-1 in almost all H/RS cells. In reactive nodes and non neoplastic cells in HL, Bob-1 IHC expression is concordant with the literature [16
]. However, in neoplastic conditions, Bob-1 positivity is restricted to LPHL and has been a useful tool in differentiating it from CHL [13
]. Only one previous study using tissue microarray, reported Bob-1+ H/RS cells in 17% of cases with strong Bob-1 positivity in only 2% of cases [21
Should the strong IHC expression of Bob-1 in H/RS cells is really to be an unexpected finding? First, in HL cell lines, Oct-2 has been reported in one study to be constantly expressed on H/RS cells [22
]. Second, a close resemblance has been found between primary mediastinal B-cell lymphoma (PMBL) and CHL [23
]. PMBL signature genes revealed an extraordinarily robust gene expression relationship between PMBL and HL, strongly supporting a pathogenetic relationship between these two lymphoma types [24
]. On IHC basis, PMBL are PAX5/BSAP+, Bob-1+, Oct-2+, PU.1+, Bcl-2+, CD30+, HLA-DR+, Bcl-6+/-, Mum-1+/- [26
], markers already identified on CHL with the exception of PU.1, Bob-1 and Oct-2 [13
]. In addition, the MAL protein initially a PMBL marker [29
], has been identified on H/RS cells from a case of NSHL in the study of Rosenwald et al [24
]. Furthermore, PMBL and HL have rearranged Ig genes but lack surface Ig [10
]. Considering these previous findings together with the results of our research, one can conclude that the expression of Bob-1 in the Egyptian population is not an uncommon finding.
What could be the other explanations of Bob-1+H/RS cells in the present study? It has been speculated that EBV contributes to the transformation and maintenance of H/RS cells, by rescuing them from apoptosis. This has been attributed to the oncogenic potential of LMP-1 on B cells through upregulation of anti-apoptosis genes including bcl-2 [30
], downregulation of p16INK4a [31
] and activation of NFκB [32
]. What is the relation between EBV and Bob-1? NFκB and Bob-1 are transcription factors required for mouse B cell differentiation, serum IgM production, late B cell maturation and function [33
]. It seems that the activation of NFκB in EBV positive cases is associated with up regulation of Bob-1 since there is a close association between the expression of Bob-1 and EBV in the present study.
In conclusion, this study confirms the nuclear expression of Bob-1 on H/RS cells in CHL, making the utility of Bob-1 to differentiate between LPHL and CHL difficult. These points open questions concerning environmental factors especially early EBV infection in developing countries and to lesser extent genetic ones. Is there truly a difference between Western and Egyptian CHL, or no differences actually exist as most researchers are more concentrated on their own Western-based populations? We feel that our work necessitates cooperative studies between different countries to answer these questions.