Bcl-6 and Bcl-2 protein expression in diffuse large B-cell lymphoma and follicular lymphoma: correlation with 3q27 and 18q21 chromosomal abnormalities.
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.
Department of Pathology, British Columbia Cancer Agency, Vancouver General Hospital, Canada.
B F
BF
Skinnider
D E
DE
Horsman
B
B
Dupuis
R D
RD
Gascoyne
D002869:Chromosome Aberrations; D025063:Chromosome Disorders; D002887:Chromosomes, Human, Pair 18; D002893:Chromosomes, Human, Pair 3; D004268:DNA-Binding Proteins / Q000096:biosynthesis*; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D016393:Lymphoma, B-Cell / Q000235:genetics / Q000378:metabolism*; D008224:Lymphoma, Follicular / Q000235:genetics / Q000378:metabolism*; D016403:Lymphoma, Large B-Cell, Diffuse / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis*; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors / Q000096:biosynthesis*; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors