Analysis Aurora-A Kinase Expression in Hodgkin and Reed-Sternberg Cells of Classical Hodgkin Lymphoma: Implications in the Regulation of G2/M Phase of Cell Cycle
R Kanagal Shamanna, N Lehman, KV Inamdar. Henry Ford Hospital, Detroit, MI
Background: Accumulating evidence suggests that the characteristic multinucleation of the Hodgkin's and Reed-Sternberg (H/RS) cells of classical Hodgkin lymphoma (cHL) results from profound alteration of cell cycle regulating proteins in the G1/S as well as G2/M phases. With respect to the later, recent studies report that the H/RS cells frequently exhibit S-phase disorder, aneuploidy and defective mitoses. Cyclin A and B1, the key regulators of G2/M transition are frequently altered in these cells. Aurora-A (AA) a Ser/Thr kinase, is also a key regulator of G2/M phase, controlling spindle assembly and centrosome separation. Altered expression AA has been implicated in the tumorigenesis of several non-Hodgkin lymphomas but its role in the pathogenesis of cHL has not been studied to date.
Design: We assessed 32 cases of cHL (between 2003 and 2009) for AA expression by immunohistochemistry. Cases selected after careful histopathologic analysis had significant numbers of morphologically typical H/RS in all cases examined. Cases comprised of cHL nodular sclerosis (n=22) and mixed cellularity (n=10) subtypes defined by the WHO classification. A mouse monoclonal AA-antibody was used (Bethyl Labs, USA). The tumor cells were scored for cytoplasmic and /or nuclear expression of AA and each case was also semi-quantitatively graded for staining intensity (1-3+).
Results: AA was detected in all cases of cHL (32/32, 100%). AA was more commonly expressed in the cytoplasm of H/RS cells [ 20/32 (62.5%) cases] than in the nucleus [9/32 (28%) ]. Both nuclear and cytoplasmic expression was observed in 3/32 (9%) cases, all of which were of the NS subtype. With respect to intensity of expression, 1+ (weak) expression of AA was observed in 22/32 (68.7%) cases while 2+ or 3+ (strong) staining intensity was observed in 10/32 (31.2%) cases. All 3 cases with both nuclear and cytoplasmic AA expression has a 3+ staining intensity.
Conclusions: Altered AA expression in cHL is interesting and its differential expression in NS and MC subtypes is noteworthy and warrants further investigation. This finding is particularly important in light of reported constitutive activation of nuclear factor (NF)-kB pathway in cHL. AA regulation of NF-kB pathway may support the proliferation of H/RS cells.
Wednesday, March 24, 2010 9:30 AM
Poster Session V # 198, Wednesday Morning