Aberrant expression of cyclin a correlates with morphogenesis of reed-sternberg cells in Hodgkin lymphoma.
Reed-Sternberg (RS) cells represent a histopathologic hallmark for Hodgkin lymphoma (HL). Viral proteins may induce aberrant expression of cyclin A and lead to multinucleation in virus-infected cells. We investigated whether Epstein-Barr virus (EBV) latent membrane protein-1 (LMP1) and cyclin A are involved in the morphogenesis of RS cells. We immunohistochemically analyzed "individual" tumor cells in 34 HLs for the subcellular expression of cyclin A and HL-related markers. In LMP1+ and LMP1- HLs, multinucleated RS cells aberrantly expressed cyclin A in cytoplasm, while the mononuclear Hodgkin cells expressed cyclin A predominantly in nuclei (P < .001). No differential expression of CD15, CD30, or CD99 in HL cells was found. In vitro, EBV-LMP1 increased cytoplasmic cyclin A expression and multinucleation in an HL cell line. Therefore, the aberrant expression of cyclin A is commonly associated with RS cell morphologic features in HL, probably through LMP1 signaling or other similar mechanisms in EBV- cases.
Chang
Kung-Chao
KC
Department of Pathology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
Chang
Yao
Y
Jones
Dan
D
Su
Ih-Jen
IJ
D000328:Adult; D014408:Biomarkers, Tumor / Q000378:metabolism; D045744:Cell Line, Tumor; D019925:Cyclin A / Q000378:metabolism*; D005260:Female; D005434:Flow Cytometry; D019084:Fluorescent Antibody Technique, Indirect; D015726:Giant Cells / Q000473:pathology / Q000821:virology; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006689:Hodgkin Disease / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D006801:Humans; D008297:Male; D016539:Reed-Sternberg Cells / Q000378:metabolism / Q000473:pathology* / Q000821:virology; D012189:Retrospective Studies; D015398:Signal Transduction; D014162:Transfection; D014763:Viral Matrix Proteins / Q000032:analysis / Q000096:biosynthesis / Q000235:genetics / Q000302:isolation & purification
D014408:Biomarkers, Tumor; D019925:Cyclin A; C037662:EBV-associated membrane antigen, Epstein-Barr virus; D014763:Viral Matrix Proteins