RESUMO
BACKGROUND: Recent reports have divided diffuse large B cell lymphoma (DLBCL) into germinal centre B cell-like and activated B cell-like subgroups with implicated differences in prognosis. AIMS: To delineate the germinal centre B cell derivation group from an Asian series of DLBCLs. METHODS: Fifty four cases were analysed by polymerase chain reaction to detect the t(14;18) translocation and immunohistochemistry for BCL2, CD10, BCL6, and E2F1 expression. RESULTS: Eighteen of 54 cases had bcl2 gene rearrangement, 36 of 52 expressed BCL2, 29 of 52 expressed BCL6, 20 of 53 expressed CD10, and 18 of 53 expressed E2F1. There was a significant association between bcl2 gene rearrangement and the expression of both BCL2 and CD10. Using the minimally acceptable criteria of t(14;18) rearrangement and/or CD10 expression, 26 of 54 cases were probably germinal centre derived, in agreement with other reports. A higher proportion of cases had t(14;18) translocation, suggesting that they may be derived from transformed follicular lymphomas. E2F1 positivity did not correlate with the known germinal centre markers, even though it has recently been suggested that it may be a new GC marker. CONCLUSIONS: It may be possible to stratify patients for treatment using markers for specific lineages of B cell differentiation.
Assuntos
Centro Germinativo/patologia , Linfoma de Células B/patologia , Linfoma Difuso de Grandes Células B/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Povo Asiático/genética , Criança , Cromossomos Humanos Par 14/genética , Cromossomos Humanos Par 18/genética , Feminino , Rearranjo Gênico do Linfócito B , Genes bcl-2/genética , Humanos , Imunofenotipagem , Linfoma de Células B/genética , Linfoma de Células B/imunologia , Linfoma Difuso de Grandes Células B/genética , Linfoma Difuso de Grandes Células B/imunologia , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodos , Translocação GenéticaRESUMO
AIM: To gain more insight into the genes involved in the aetiology and pathogenesis of anaplastic large cell lymphoma (ALCL). METHODS: Serial analysis of gene expression (SAGE) was undertaken on the CD4+ALK+ (anaplastic lymphoma kinase positive) ALCL derived cell line Karpas299 and as comparison on CD4+ T cells. Quantitative reverse transcription polymerase chain reaction (RT-PCR) and immunohistochemistry were performed on five ALCL derived cell lines and 32 tissue samples to confirm the SAGE data. RESULTS: High expression of Mcl-1 was seen in the Karpas299 cell line, whereas the two other antiapoptotic Bcl-2 family members, Bcl-2 and Bcl-X(L), were not detected in the SAGE library. Quantitative RT-PCR confirmed the high expression of Mcl-1 mRNA and low expression of Bcl-2 and Bcl-X(L) in Karpas299 and in four other ALCL cell lines. To expand on these initial observations, primary tissue samples were analysed for Mcl-1, Bcl-X(L), and Bcl-2 by immunohistochemistry. All 23 ALK+ and nine ALK- ALCL cases were positive for Mcl-1. Bcl-2 and Bcl-X(L) were expressed infrequently in ALK+ ALCL cases, but were present in a higher proportion of ALK- ALCL cases. CONCLUSION: The consistent high expression of Mcl-1 in ALK+ and ALK- ALCL suggests that Mcl-1 is the main antiapoptotic protein in this disease. The high frequency of Mcl-1, Bcl-2, and Bcl-X(L) positive ALCL cases in the ALK- group compared with the ALK+ group indicates that ALK induced STAT3 activation is not the main regulatory pathway in ALCL.
Assuntos
Regulação Neoplásica da Expressão Gênica/genética , Linfoma Difuso de Grandes Células B/genética , Proteínas de Neoplasias/genética , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas c-bcl-2/genética , Quinase do Linfoma Anaplásico , Apoptose/genética , Linfócitos T CD4-Positivos/fisiologia , Linhagem Celular Tumoral , Genes bcl-2/genética , Humanos , Imuno-Histoquímica/métodos , Proteína de Sequência 1 de Leucemia de Células Mieloides , RNA Mensageiro/genética , RNA Neoplásico/genética , Receptores Proteína Tirosina Quinases , Reação em Cadeia da Polimerase Via Transcriptase Reversa/métodos , Proteína bcl-XRESUMO
AIMS: To examine the expression of the Bcl-2 family of proteins (Bcl-2, Bcl-x, Bcl-xL and Bax) in classical Hodgkin's lymphoma (cHL) and to correlate the expression of these proteins with proliferation, apoptosis and the presence of Epstein-Barr virus (EBV). METHODS AND RESULTS: Expression of the Bcl-2 family of proteins was detected by immunohistochemistry, proliferation was determined by Ki67 labelling and apoptosis by TUNEL in-situ hybridization. EBV was detected by Epstein-Barr virus early RNA (EBER) in-situ hybridization. Expression of Bcl-2, Bcl-x, Bcl-xL and Bax was detected in the Hodgkin/Reed-Sternberg (H/RS) cells in 43.7% (27/62), 87.5% (56/64), 67.2% (41/61) and 74.6% (47/63) of the cHL cases, respectively. EBER was detected in 53% (35/66) of the cases, whereas Ki67 was observed in 86.7% (52/60) of the cases. Apoptotic H/RS cells were observed infrequently, and only 43.2% (11/26) of the cases showed an apoptotic index of > or = 10% in the H/RS cells. A statistically significant inverse relationship was observed between the expression of Bcl-2 and the presence of EBV (P = 0.003). Bcl-xL showed an inverse correlation with apoptosis in the H/RS cells (P = 0.004). CONCLUSIONS: The higher Bcl-xL expression (67.2%) compared with Bcl-2 expression (43.5%) observed in cHL as well as the statistically significant inverse relationship between Bcl-xL and apoptosis suggests that Bcl-xL plays an important role in the survival of H/RS cells. Expression of Bax may be neutralized by other anti-apoptotic members of the family such as Bcl-2 and/or Bcl-xL.
Assuntos
Herpesvirus Humano 4/isolamento & purificação , Doença de Hodgkin/virologia , Proteínas Proto-Oncogênicas c-bcl-2/biossíntese , Células de Reed-Sternberg/virologia , Infecções Tumorais por Vírus/patologia , Antígenos CD/biossíntese , Apoptose , Morte Celular , Divisão Celular , Doença de Hodgkin/metabolismo , Doença de Hodgkin/patologia , Humanos , Imuno-Histoquímica , Imunofenotipagem , Hibridização In Situ , Marcação In Situ das Extremidades Cortadas , Antígeno Ki-67/metabolismo , Proteínas Proto-Oncogênicas/biossíntese , Proteínas de Ligação a RNA/biossíntese , Células de Reed-Sternberg/metabolismo , Células de Reed-Sternberg/patologia , Proteínas Ribossômicas/biossíntese , Infecções Tumorais por Vírus/metabolismo , Proteína X Associada a bcl-2 , Proteína bcl-XRESUMO
Lymphomas, ranked twelve among all cancers world-wide in the 1990s, in which it is more prevalent in males compared to females. A previous study on lymphomas in East Malaysia for a period of 3 years from 1981-1983 showed that the pattern of lymphomas conformed to the general pattern observed in Asia. Current study reviews lymphoma cases from the Department of Pathology, Queen Elizabeth Hospital, Sabah between 1997 and 1999, with the aim of investigating if the spectrum and pattern in Sabah has since changed, a decade later. A total of 91 confirmed lymphoma cases were phenotyped with a panel of antibodies and classified using the new WHO proposed list of lymphoid neoplasms. The 1981-1983 series was reviewed and cases reclassified accordingly for comparison. There are 83 (91.2%) NHL and 8 (8.8%) HL cases in this series, a ratio of NHL to HL of 9:1. Of the 83 cases of NHL, 66 (79.5%) were confirmed B-cell type, 13 (15.7%) T-phenotype, 1(1.2%) null cell type and one case unclassified. Diffuse large B-cell lymphoma is the most prevalent, (65.1%), followed by Burkitt's lymphoma and follicular lymphoma, (10.6%) each. Lymphoma pattern concurs with the previous series from Sabah, with higher prevalence of diffuse large cell lymphoma and lower incidence of follicular lymphoma and HL, as seen elsewhere in Asia. There is an overall increase in the number of cases of NHL in the 1990s. However, the proportion of T-NHL is reduced when compared to the series in the 1980s.