MABF1993-100UG Sigma-AldrichAnti-CD30 Antibody, clone CON6D/B5

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of malignant lymphoma. The incidence of Epstein-Barr virus (EBV)-positive DLBCL in Asian and Latin American countries ranges from 8 to 10%. The prognosis of patients with EBV-positive DLBCL is controversial. To compare the clinical outcome of EBV-positive and EBV-negative patients with DLBCL in the rituximab era, we analyzed 239 patients with de novo DLBCL diagnosed between January 2007 and December 2011. The presence of EBV in lymphoma cells was detected using EBV-encoded RNA in situ hybridization, and it was found that 18 (6.9%) of 260 patients with diagnosed DLBCL tested positive. Among the 260 cases, 216 cases were treated with rituximab plus chemotherapy, as were 8 EBV-positive DLBCL patients. The median overall survival and progression-free survival times in patients with EBV-positive DLBCL were 8.7 months and 6.8 months, respectively. The median overall survival and progression-free survival could not be determined in EBV-negative DLBCL patients (P = 0.0002, P < 0.0001, respectively). The outcome of patients with EBV-positive DLBCL remains poor, even in the rituximab era.

Immunohistochemical evaluation of CD30 expression is commonly performed in the assessment of hematopoietic disorders and germ cell tumors. A new monoclonal antibody, CON6D/B5, directed against the CD30 antigen has become commercially available for use in formalin-fixed paraffin-embedded tissue samples. The performance characteristics of CON6D/B5 were tested and compared with the well-characterized monoclonal CD30 antibody Ber-H2. Among the various neoplasms analyzed, there was complete concordance between the results of CON6D/B5 and Ber-H2 staining. Similar to Ber-H2, CON6D/B5 immunoreactivity was observed in all cases of classical Hodgkin lymphoma, anaplastic large cell lymphoma, and embryonal carcinoma, with no staining detectable in any of the other various tumors evaluated, including several neoplasms earlier reported as showing CD30 positivity by other investigators. The labeling intensity was much stronger with CON6D/B5 compared with Ber-H2, although no significant differences were observed with regard to the numbers of positively labeled cells in individual cases. The monoclonal antibody CON6D/B5 offers a suitable alternative to Ber-H2 for the immunohistochemical detection of CD30 expression.

The existence, diagnostic features, and the biological and clinical relevance of lymphocyte-rich classical Hodgkin's lymphoma remain controversial. A comparative marker analysis of lymphocyte-rich classical Hodgkin's lymphoma, nodular lymphocyte-predominance Hodgkin's lymphoma, and of other subtypes of classical Hodgkin's lymphoma was carried out. Markers were selected focusing on B-cell lineage and transcription program (OCT.1, OCT.2, BOB.1, BCL6, PAX-5, GCET1, KLHL6, and BLIMP1), the NF-kappaB signaling pathway (REL-B, C-REL, TRAF-1, p-50, and MUM-1) and the T-cell microenvironment (CD3, CD57, PD-1, CXCL-13, and CD10, BCL-6, CD23). Lymphocyte-rich classical Hodgkin's lymphoma cases displayed features intermediate between those of classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma. The expression of B-cell transcription factors such as OCT.1, OCT.2, BOB.1, and BCL6 was more frequent in lymphocyte-rich classical Hodgkin's lymphoma than in classical Hodgkin's lymphoma. A follicular T-cell microenvironment was also identified in 50% of lymphocyte-rich classical Hodgkin's lymphoma cases. NF-kB markers were expressed at frequencies comparable with those observed in classical Hodgkin's lymphoma. The neoplastic cell immunophenotype and microenvironment in lymphocyte-rich classical Hodgkin's lymphoma closely mimic that which are observed in the outer zone of the germinal center, where B-cell blasts with germinal-center markers co-express CD30 and the B-cell transcription program, surrounded by follicular T-cell rosettes. Lymphocyte-rich classical Hodgkin's lymphoma seems to be characterized by a stronger expression of the B-cell transcription program by the neoplastic cells and by a follicular T-cell background, occupying an intermediate position between classical Hodgkin's lymphoma and nodular lymphocyte-predominance Hodgkin's lymphoma.

The positive regulatory domain I (PRDM1) protein or BLIMP-1, belonging to the PRDM gene family of transcriptional repressors, is a key regulator of terminal differentiation in B-lymphocytes and is critical for plasma cell differentiation.Here we document the expression of PRDM1 in normal and neoplastic lymphoid cells, through the use of a monoclonal antibody that recognizes the molecule in paraffin-embedded tissue sections. A large series of B and T-cell lymphomas (679 cases) was studied, using tissue microarrays.Multiple myeloma, plasmacytoma and lymphoplasmacytic lymphoma cases (n=19) were positive. Plasmablastic lymphoma, oral mucosa-type (n=15), were also found to be positive. PRDM1 protein was expressed in some cases of B-cell neoplasia, i.e. chronic lymphocytic leukemia/small lymphocytic lymphoma (15%), diffuse large B-cell lymphoma (43%), classical Hodgkin's lymphoma (41%) and also in T-cell lymphoma (23%).Most B-neoplastic cells showing plasmablastic differentiation were PRDM1-positive. Unexpectedly, a subset of diffuse large B-cell lymphoma expressed PRDM1, lacked detectable plasmablastic or immunoblastic changes and displayed more aggressive behavior, with a shorter failure-free survival. In contrast to normal B-cells, diffuse large B-cell lymphoma cases with increased PRDM1 expression co-expressed BCL-6 and MUM1/IRF4, confirming that PRDM1 expression in these tumors is insufficient to drive the full genetic program associated with plasmacytic differentiation.