Aurora-A and Polo-Like Kinases are Important Diagnostic and Therapeutic Markers in Hodgkin Lymphoma and Mimics
Madhu P Menon
Henry Ford Health System
Background: Aurora-A (AA) and Polo-like kinases (PLK) are mitotic kinases that regulate the G2/M phase of the cell cycle. It has been demonstrated that AA acts as an upstream regulator of PLK, mediati..more »
Background: Aurora-A (AA) and Polo-like kinases (PLK) are mitotic kinases that regulate the G2/M phase of the cell cycle. It has been demonstrated that AA acts as an upstream regulator of PLK, mediating its phosphorylation in the presence of a cofactor named Bora. PLK is activated by AA to promote checkpoint recovery in mitosis. AA and PLK are implicated in the tumorigenesis of solid tumors, and, recently, in B- and T-cell non Hodgkin lymphomas (NHL). They play a key role in tumor proliferation and disease progression in highly aggressive B-cell NHL. They also serve as indicators of disease activity and are thus attractive potential therapeutic targets. Expression of AA and/or PLK has not yet been assessed in Classic Hodgkin Lymphoma (CHL) and its mimics. This study assesses AA and PLK expression in different CHL types, such as nodular sclerosis type, mixed cellularity type, and lymphocyte rich type, and their mimics: nodular lymphocyte predominant Hodgkin lymphoma (NLPHL) and primary mediastinal B-cell lymphoma (PMBL).Design:We assessed 27 CHL cases, 16 NLPHL cases, and 8 PMBL cases for AA and PLK expression by immunohistochemistry. CHL cases included the following: 8 mixed cellularity CHL, 1 lymphocyte rich CHL, and 18 nodular sclerosis CHL. A mouse monoclonal AA-antibody (1:1000 dilution, Abcam, UK) and a PLK-antibody (1:500 dilution, Cell Signaling Technologies, USA) were used. Each case was semi-quantitatively graded for percentage of positive cells (50%), for staining intensity (1-3+), and for localization (nuclear vs. cytoplasmic). Immunohistochemical analysis was performed independently by 2 pathologists (KMH and KVI). Statistical analysis was performed using Fisher's exact test.Results:AA was expressed in 100% of CHL and NLPHL cases. AA stained predominantly cytoplasm of tumor cells in both NLPHL and CHL. PLK was expressed in 100% of NLPHL and 96% of CHL cases (1 mixed cellularity type CHL did not stain for PLK). PLK showed both nuclear and cytoplasmic staining for both NLPHL and CHL. In contrast, only 37% of PMBL cases were positive for AA and PLK (Table 1). In the CHL group, cases with more than 50% of tumor cells expressing PLK tended to present with higher stage and extranodal disease. In the NLPHL group, PLK correlated with higher stage (III-IV) disease at presentation (p=0.044). No statistically significant differences were found in either intensity or localization of AA or PLK within or between NLPHL and CHL cohorts.Aurora-A PositiveAurora-A NegativePLK PositivePLK NegativeClassic Hodgkin Lymphoma270261Nodular Lymphocyte Predominant Hodgkin Lymphoma160160Primary Mediastinal B-cell Lymphoma3535Table 1. AA and PLK positivity in CHL, NLPHL, and PMBL.AA was expressed in CHL but not PMBL (p=0.0002)PLK was expressed in CHL but not PMBL (p=0.0009)AA was expressed in NLPHL but not PMBL (p=0.0013)PLK was expressed in NLPHL but not PMBL (p=0.0013). Conclusion: AA and PLK are commonly expressed in CHL and NLPHL but not in PMBL. Thus, they are useful markers in the distinction of CHL or NLPHL from PMBL. PLK is a useful marker for the prognostication of NLPHL. AA and PLK are attractive potential therapeutic targets in the treatment of CHL and NLPHL. Additional studies are underway to characterize an array of hematopoietic lesions known to overlap with CHL.
Henry Ford Hospital
Resident PGY 2
Henry Ford Health System