Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: Correlation with 3q27 and 18q21 chromosomal abnormalities

• Published in: Human pathology Vol. 30; no. 7; pp. 803 - 808
• Main Authors: Skinnider, Brian F, Horsman, Douglas E, Dupuis, Beverley, Gascoyne, Randy D
• Format: Journal Article
• Language: English
• Published: New York, NY Elsevier Inc 01.07.1999; Elsevier
• Subjects: bcl-2; bcl-6; Biological and medical sciences; chromosome 18; chromosome 3; Chromosome Aberrations; Chromosome Disorders; Chromosomes, Human, Pair 18; Chromosomes, Human, Pair 3; DNA-Binding Proteins - biosynthesis; Gene Expression; Hematologic and hematopoietic diseases; Humans; Immunohistochemistry; Leukemias. Malignant lymphomas. Malignant reticulosis. Myelofibrosis; Lymphoma; Lymphoma, B-Cell - genetics; Lymphoma, B-Cell - metabolism; Lymphoma, Follicular - genetics; Lymphoma, Follicular - metabolism; Lymphoma, Large B-Cell, Diffuse - genetics; Lymphoma, Large B-Cell, Diffuse - metabolism; Medical sciences; Proto-Oncogene Proteins - biosynthesis; Proto-Oncogene Proteins c-bcl-2 - biosynthesis; Proto-Oncogene Proteins c-bcl-6; Transcription Factors - biosynthesis; Translocation, Genetic; DLBCL; bcl-2; NHL; FL; bcl-6; chromosome 3; AIDS; Lymphoma; chromosome 18; MALT; Chromosomal aberration; Human; Immunohistochemistry; Germinative center; Malignant hemopathy; B-Lymphocyte; Large cell lymphoma; Non Hodgkin lymphoma; Chromosome 3; Gene expression; Carcinogenesis; Pathology; Lymphoproliferative syndrome; Follicular lymphoma; Lymphatic follicle; Molecular biology; Apoptosis; Chromosome 18
• ISSN: 0046-8177; 1532-8392
• DOI: 10.1016/S0046-8177(99)90141-7

The bcl-2 gene on chromosome 18 at q21 and the bcl-6 gene on chromosome 3 at q27 are both highly regulated during B-cell differentiation and show an inverse relationship of expression in the normal secondary lymphoid follicle. The objective of this study was to investigate the relationship between bcl-2 and bcl-6 protein expression and the relationship between protein expression and the corresponding chromosomal alterations in malignant lymphomas, including those associated with the germinal center. Expression of bcl-2 and bcl-6 proteins was studied in 55 cases of diffuse large B-cell lymphoma (DLBCL) and 21 cases of follicular lymphoma (FL), and the results correlated with the presence of t(14;18) and 3q27 abnormalities in a subset of 52 cases with cytogenetic analysis. These cases were selected to represent a spectrum of nodal and extranodal lymphomas, including those with and without a t(14;18). It was shown that the neoplastic cells in 71% of DLBCLs and 100% of FLs expressed bcl-6 protein. Expression of bcl-6 was seen more frequently in diffuse large B-cell lymphomas with large noncleaved morphology compared with immunoblastic morphology (82% v 27%, P = .0015), but failed to correlate with 3q27 abnormalities. Thirty-eight percent of cases with 3q27 abnormalities were bcl-6 protein negative, whereas 85% of cases without a 3q27 abnormalities were bcl-6 protein positive. Expression of bcl-2 protein was shown in 51% DLBCLs (nodal v extranodal, 71% v 30%, P = .012). bcl-2 protein was expressed in 89% of FLs with t(14;18), in contrast to 25% of FLs without t(14;18) ( P = .016). In DLBCL and FL with t(14;18), the most common pattern of expression was bcl-2 + bcl-6 + . In lymphomas without t(14;18), there was not an inverse relationship between bcl-2 and bcl-6 protein expression. In conclusion, these data suggest that mechanisms other than gene rearrangements can deregulate bcl-2 and bcl-6 expression in lymphomas, and there does not appear to be an inverse relationship between these two proteins as seen in the normal germinal center.