ABSTRACT
CD30 expression in peripheral T-cell lymphoma (PTCL) and angioimmunoblastic T-cell lymphoma (AITL) is currently of great interest because therapy targeting CD30 is of clinical benefit, but the clinical and therapeutic relevance of CD30 expression in these neoplasms still remains uncertain. The aim of this study was to better quantify CD30 expression in AITL and PTCL-not otherwise specified (NOS). The secondary objective was to determine whether CD30 cells exhibit a B-cell or a T-cell phenotype. Gene expression profiling was studied in a series of 37 PTCL cases demonstrating a continuous spectrum of TNFRSF8 expression. This prompted us to study CD30 immunohistochemical (IHC) expression and mRNA levels by reverse transcription polymerase chain reaction (RT-PCR) in a different series of 51 cases (43 AITLs and 8 PTCL-NOSs) in routine samples. Double stainings with PAX5/CD30, CD3/CD30, and LEF1/CD30 were performed to study the phenotype of CD30 cells. Most (90%) of the cases showed some level of CD30 expression by IHC (1% to 95%); these levels were high (>50% of tumoral cells) in 14% of cases. CD30 expression was not detected in 10% of the cases. Quantitative RT-PCR results largely confirmed these findings, demonstrating a moderately strong correlation between global CD30 IHC and mRNA levels (r=0.65, P=1.75e-7). Forty-four of the positive cases (98%) contained CD30-positive B cells (PAX5), whereas atypical CD30-positive T cells were detected in 42 cases (93%). In conclusion, our data show that most AITL and PTCL-NOS cases express CD30, exhibiting very variable levels of CD30 expression that may be measured by IHC or RT-PCR techniques.
Subject(s)
B-Lymphocytes/immunology , Biomarkers, Tumor/analysis , Immunoblastic Lymphadenopathy/immunology , Ki-1 Antigen/analysis , Lymphoma, T-Cell, Peripheral/immunology , Lymphoma, T-Cell/immunology , T-Lymphocytes/immunology , B-Lymphocytes/pathology , Biomarkers, Tumor/genetics , Biopsy , Gene Expression Profiling , Humans , Immunoblastic Lymphadenopathy/genetics , Immunoblastic Lymphadenopathy/pathology , Immunohistochemistry , Immunophenotyping , Ki-1 Antigen/genetics , Lymphoma, T-Cell/genetics , Lymphoma, T-Cell/pathology , Lymphoma, T-Cell, Peripheral/genetics , Lymphoma, T-Cell, Peripheral/pathology , Phenotype , RNA, Messenger/genetics , Reverse Transcriptase Polymerase Chain Reaction , T-Lymphocytes/pathologyABSTRACT
MYD88 L265P is a somatic mutation that has been identified in about 90% of Waldenström macroglobulinemia/lymphoplasmacytic lymphomas (LPLs). It has also been detected in a subset of marginal zone lymphoma (MZL) cases, but the frequency and clinical and histologic features of these mutated MZL cases has only been partially characterized. We have developed a customized TaqMan allele-specific polymerase chain reaction for sensitive detection of this mutation in paraffin-embedded tissue. We analyzed samples from 19 patients with LPL, 88 patients with splenic marginal zone lymphoma (SMZL), 8 patients with nodal marginal zone lymphoma (NMZL), 21 patients with extranodal mucosa-associated lymphoid tissue (MALT), and 2 patients with B-cell lymphoma not otherwise specified. By integrating mutational, histologic, and clinical data, 5 cases were reclassified as LPL. After reclassification, MYD88 L265P was detected in 13/86 (15%) SMZL and in 19/24 LPL (79%) cases. The mutation was absent from NMZL and MALT cases. A strong correlation was found between the presence of an IgM monoclonal paraproteinemia and the MYD88 L265P mutation (P<0.0001). SMZL cases positive for MYD88 L265P were also associated with monoclonal IgM paraproteinemia (4/13 cases; P<0.0283), although with less serum paraproteinemia. They also had a higher frequency of plasmacytic differentiation (9/13) but with no correlation between the presence of mutation and of light chain-restricted plasma cells in tissue. Demonstration of the MYD88 L265 mutation is a valuable tool for the diagnosis of LPL, although some SMZL cases carrying the mutation do not fulfill the diagnostic criteria for LPL.
