Human Polycomb-group (PcG) genes play a crucial role in the regulation of 
embryonic development and regulation of the cell cycle and hematopoiesis. PcG 
genes encode proteins that form two distinct PcG complexes, involved in 
maintenance of cell identity and gene silencing patterns. We recently showed 
that expression of the BMI-1 and EZH2 PcG genes is separated during normal 
B-cell development in germinal centers, whereas Hodgkin/Reed-Sternberg (H/RS) 
cells co-express BMI-1 and EZH2. In the current study, we used 
immunohistochemistry and immunofluorescence to determine whether the binding 
partners of these PcG proteins are also present in H/RS cells and H/RS-derived 
cell lines. PcG expression profiles were analyzed in combination with expression 
of the cell cycle inhibitor p16INK4a, because experimental model systems 
indicate that p16 is a downstream target of Bmi-1. We found that H/RS cells and 
HL-derived cell lines co-express all core proteins of the two known PcG 
complexes, including BMI-1, MEL-18, RING1, HPH1, HPC1, and -2, EED, EZH2, YY1, 
and the HPC2 binding partner, CtBP. Expression of HPC1 has not been found in 
normal mature B cells and other malignant lymphomas of B-cell origin, suggesting 
that the PcG expression profile of H/RS is unique. In contrast to Bmi-1 
transgenic mice where p16INK4a is down-regulated, 27 of 52 BMI-1POS cases of HL 
revealed strong nuclear expression of p16INK4a. We propose that abnormal 
expression of BMI-1 and its binding partners in H/RS cells contributes to 
development of HL. However, abnormal expression of BMI-1 in HL is not 
necessarily associated with down-regulation of p16INK4a.