Aurora-A Kinase Distinguishes ALK+ Anaplastic Large Cell Lymphoma from ALK Negative and Cutaneous ALCL among Other T-Cell Lymphomas: Analysis of 72 Cases
RK Shamanna, LJ Medeiros, L Whiteley, DS Schultz, DA Chitale, KV Inamdar. Henry Ford Hospital, Detroit, MI; The University of Texas MD Anderson Cancer Center, Houston, TX
Background: Aurora-A kinase (AA), a cell cycle-regulating Ser/Thr kinase, plays a key role in the tumorigenesis of a variety of solid tumors as well as highly aggressive B-cell non-Hodgkin lymphoma (NHL). Expression of AA has not been assessed to date in T- NHL. Thus, we performed this study to assess AA expression in a variety of T-cell lymphoma types.
Design: We assessed 72 T-cell NHL for AA expression by immunohistochemistry (Table). A mouse monoclonal AA-antibody was used (Bethyl Labs, USA). Any cytoplasmic and/or nuclear staining was considered positive. Each case was semi-quantitatively graded for percentage of positive cells (0-25%; 25-50%; >50%) and staining intensity (1-3+). AA mRNA expression was also assessed by real-time quantitative reverse transcriptase Polymerase Chain Reaction (RT-PCR) in 9 ALCL and 9 PTCL, NOS cases.
Results: AA was detected in 48/72 (67%) T-NHL; most frequently in ALKpositive (ALK+)ALCL (100%) and peripheral T-cell lymphoma, not otherwise specified (PTCL, NOS) (100%) compared with other T-NHL. AA expression was primarily cytoplasmic in ALK+ALCL and predominantly nuclear in other T-NHL types (p=<0.001). In the ALCL group, ALK+ ALCL more frequently had cytoplasmic AA compared with ALK negative (ALK-) (p<0.001) or cutaneous ALCL (c-ALCL) (p<0.001). 2+ or 3+ staining intensity was more frequent in ALK+ (67%) compared with ALK- (9%, p=0.03) or c-ALCL (43%, p=0.05). ALK+ALCL (55.6%) more frequently had >50% positive tumor cells than c-ALCL (0%) (p=0.0264). RT-PCR revealed higher AA mRNA expression in ALK+ ALCL compared with ALK-, c-ALCL or PTCL, NOS cases.
|ALK -||8 (73)||25||75|
|Mycosis Fungoides||4 (67)||0||100|
|Extranodal NK/T cell, nasal type||3 (50)||0||100|
|Subcutaneous panniculitis-like||1 (33.3)||0||100|
Conclusions: AA is a useful marker for distinction of AKL+ ALCL from ALK- and c-ALCL. Its overexpression in ALK+ ALCL implicates a key role in the pathobiology of ALCL. AA might be a molecular target for treatment of T-NHL.
Monday, March 9, 2009 9:30 AM
Poster Session I Stowell-Orbison/Autopsy Award # 191, Monday Morning