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

Hum Pathol. 1999 Jul;30(7):803-8. 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.

MeSH terms

  • Chromosome Aberrations
  • Chromosome Disorders
  • Chromosomes, Human, Pair 18
  • Chromosomes, Human, Pair 3
  • DNA-Binding Proteins / biosynthesis*
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • 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*
  • Proto-Oncogene Proteins / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis*
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors / biosynthesis*
  • Translocation, Genetic


  • DNA-Binding Proteins
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-bcl-6
  • Transcription Factors