RESUMO
The oncogene c-Maf was recently found to be overexpressed in approximately 50% of multiple myeloma cases, and a role for c-Maf in promoting cyclin D2 expression has been postulated. We previously examined c-Maf expression in various T-cell lymphomas by reverse-transcription polymerase chain reaction and found extremely elevated c-Maf levels in angioimmunoblastic T-cell lymphoma (AILT). In this study, we examined T-cell lymphomas for c-Maf and cyclin expression immunohistochemically. Of 93 cases of T-cell lymphomas we investigated in the current study, c-Maf expression was seen in 23 out of 31 cases of AILT, 3 out of 11 of adult T-cell leukemia/lymphoma, 4 out of 19 of peripheral T-cell lymphoma, unspecified [PTCL(U)], and 0 out of 11 cases of mycosis fungoides, 0 out of 11 of anaplastic large cell lymphoma, and 1 out of 10 of extranodal NK/T-cell lymphoma, nasal type. Double immunostaining in AILT revealed that the majority of c-Maf-positive cells were also positive for CD43 (MT1), CD45RO (UCHL-1), and CD4 but were negative for CD20 (L26). Additionally, cyclins D1 and D2, which stimulate cell cycle progression, were overexpressed in a large number of the c-Maf-positive AILT samples. Quantitative reverse-transcription polymerase chain reaction analysis also showed that c-Maf was overexpressed in 8/31 cases of AILT, 0/19 cases of PTCL(U), 0/11 cases of anaplastic large cell lymphoma, 0/10 cases of extranodal NK/T-cell lymphoma, nasal type, and 2/8 cases of multiple myeloma, presenting significant difference between AILT and PTCL(U) (P=0.016, chi test). These findings strongly suggest that CD4-positive neoplastic T cells in AILT show c-Maf expression and provide new insight into the pathogenesis of AILT suggesting c-Maf to be a useful diagnostic marker for AILT.
Assuntos
Biomarcadores Tumorais/análise , Linfadenopatia Imunoblástica/metabolismo , Linfoma de Células T/química , Proteínas Proto-Oncogênicas c-maf/análise , Adulto , Antígenos CD20/análise , Biomarcadores Tumorais/genética , Antígenos CD4/análise , Ciclina D , Ciclina D2 , Ciclinas/análise , Humanos , Linfadenopatia Imunoblástica/genética , Linfadenopatia Imunoblástica/patologia , Imuno-Histoquímica , Antígenos Comuns de Leucócito/análise , Leucossialina/análise , Linfoma de Células T/genética , Linfoma de Células T/patologia , Proteínas Proto-Oncogênicas c-maf/genética , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para CimaRESUMO
We measured T-cell intracellular antigen-1 (TIA-1) expression in neoplastic cells from patients with hairy cell leukemia. Five of nine cases were positive for cytoplasmic TIA-1, with a small, dot-like, granular expression pattern. However, neoplastic cells were granzyme B- and perforin- negative in all cases. Other positive markers were CD20 in 9/9 cases, CD19 in 9/9 cases, DBA44 in 8/9 cases, LeuM5(CD11C) in 8/9 cases, IL-2R(CD25) in 7/9 cases, CD103 in 7/9 cases, FMC7 in 6/9 cases, and tartrate- resistant acid phosphatase in 5/7 cases. We also analyzed TIA-1 expression in 94 B cell lymphomas, including 19 diffuse, large cell lymphomas, 19 mantle cell lymphomas, six follicular lymphomas, two extranodal marginal zone B-cell lymphomas, 13 nodal marginal zone B-cell lymphomas, one mediastinal large-cell lymphoma, 19 diffuse small-cell lymphomas, 14 myelomas, and one splenic lymphoma with villous lymphocytes. All cases were negative for TIA-1 expression. Based on these findings, TIA-1 expression in neoplastic cells of low-grade B-cell lymphomas may be a good diagnostic marker for hairy cell leukemia. Moreover, TIA-1 reactivity in lymphomas does not necessarily indicate a T- or NK-cell derivation.
