Centrosome aberrations as a possible mechanism for chromosomal instability in non-Hodgkin's lymphoma.
Recently, centrosome aberrations have been described as a possible cause of aneuploidy in many solid tumors. To investigate whether centrosome aberrations occur in non-Hodgkin's lymphoma (NHL) and correlate with histologic subtype, karyotype, and other biological disease features, we examined 24 follicular lymphomas (FL), 18 diffuse large-B-cell lymphomas (DLCL), 33 mantle cell lymphomas (MCL), and 17 extranodal marginal zone B-cell lymphomas (MZBCL), using antibodies to centrosomal proteins. All 92 NHL displayed numerical and structural centrosome aberrations as compared to nonmalignant lymphoid tissue. Centrosome abnormalities were detectable in 32.3% of the cells in NHL, but in only 5.5% of lymphoid cells from 30 control individuals (P<0.0001). Indolent FL and MZBCL contained only 25.8 and 28.8% cells with abnormal centrosomes. In contrast, aggressive DLCL and MCL harbored centrosome aberrations in 41.8 and 35.0% of the cells, respectively (P<0.0001). Centrosomal aberrations correlated to lymphoma grade, mitotic, and proliferation indices, but not to the p53 labeling index. Importantly, diploid MCL contained 31.2% cells with abnormal centrosomes, while tetraploid samples harbored centrosome aberrations in 55.6% of the cells (P<0.0001). These results indicate that centrosome defects are common in NHL and suggest that they may contribute to the acquisition of chromosomal instability typically seen in NHL.
Krämer
A
A
Medizinische Klinik und Poliklinik V, Universität Heidelberg, Heidelberg, Germany.
Schweizer
S
S
Neben
K
K
Giesecke
C
C
Kalla
J
J
Katzenberger
T
T
Benner
A
A
Müller-Hermelink
H K
HK
Ho
A D
AD
Ott
G
G
D002455:Cell Division; D018385:Centrosome / Q000473:pathology*; D002869:Chromosome Aberrations; D002873:Chromosome Fragility; D004171:Diploidy; D016158:Genes, p53; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008214:Lymphocytes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000473:pathology; D008228:Lymphoma, Non-Hodgkin / Q000145:classification / Q000235:genetics* / Q000473:pathology; D008940:Mitotic Index; D014066:Palatine Tonsil / Q000473:pathology; D011123:Polyploidy; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
D016159:Tumor Suppressor Protein p53