Correlation Between Cytogenetic Aberrations Detected by Conventional Chromosome Banding Analysis and Specific Immunophenotypes in Patients with B-Cell Lymphoproliferative Diseases
Authors: Kern Wolfgang , Haferlach Torsten , Schnittger Susanne , Haferlach Claudia 
Published: April 2020

Abstract
While typical cytogenetic aberrations and immunophenotypes, respectively, have been identified in distinct entities of B-cell lymphoproliferative diseases (B-LPD) their specificity is not complete in every case. Thus, the t(14;18), which is characteristic of follicular lymphoma, is present also in cases with other B-LPD. Furthermore, expression of CD5 can be observed in cases with B-LPD other than mantle cell lymphoma and chronic lymphocytic leukemia. Moreover, a variety of chromosome aberrations has been described which has not yet been assigned to distinct B-LPD subentities. Accordingly, immunophenotypes are not clear-cut for distinct B-LPD subentities but rather overlap with regard to some features, e.g. between marginal zone lymphoma and lymphoplasmacytic lymphoma. The aim of the present study therefore has been to characterize cases with B-LPD (excluding B-CLL) by conventional chromosome analysis and by multiparameter immunophenotyping and to assess whether and to which degree relations between the results of both methods exist. A total of 346 patients have been evaluated. The frequencies of the respective chromosomal aberrations were (more than one aberration occurred in some cases): t(8;14), 16 (4.6%); t(11;14) without additional aberrations, 10 (2.9%); t(11;14) with additional aberrations, 43 (12.4%); trisomy 12, 48 (13.9%); t(14;18), 18 (5.2%); t(14;19), 6 (1.7%); trisomy 3, 23 (6.6%); trisomy 8, 3 (0.9%); del7q, 9 (2.6%); del13q, 30 (8.7%); 17p-, 30 (8.7%); complex (≥3) aberrations, 58 (16.8%) while a normal karyotype was found in 126 (36.4%) cases. The comparison with immunophenotypes revealed various previously reported findings like the stronger expression of CD10 in cases with t(8;14) (33.4 vs. 14.6%, p=0.001) and of CD5 in cases with t(11;14) (73.3 vs. 48.4%, p&lt;0.001). Furthermore, the respective chromosome aberrations were found to be associated with a significantly (p&lt;0.05 for all comparisons) higher(+)/lower(−) expression of the following antigens: t(8;14), CD10+CD38+CD25+; t(14;18), CD10+CD11c−; t(11;14) with additional aberrations, CD38+CD20+CD22+CD5+CD 79b+FMC7+IgM+; t(11;14) without additional aberrations, CD22+; t(14;19), CD11c+; 17p−, CD38−CD22+CD79b+FMC7+CD11c+; trisomy 12, CD25+CD5+CD10−CD23+; del13q, CD25+CD20+CD22+CD5+CD79b+CD11c−; del7q, CD25−; complex aberrations, CD20+CD22+CD79b+; trisomy 8, CD5−. Accordingly, regarding the whole series distinct antigens were found coexpressed at high frequencies. Specifically, highly significant positive correlations (p&lt;0.001, r&gt;0.5) were found between CD20, CD22, CD79b, and FMC7. In contrast, the expression of CD10 was highly significantly negatively related (p&lt;0.001, r&lt;−0.2) to the expression of CD11c and CD5. Overall, however, there was no complete positive or negative correlation between any of the antigens analyzed with regard to their respective expression intensities. Hierarchical cluster analysis has been performed to assess correlations between the expression intensities of distinct antigens on the one hand and distinct chromosome aberrations on the other hand. While the majority of cases with t(11;14) clustered rather closely together, cases with other chromosome aberrations were distributed more heterogeneously. These data suggest that there are significant correlations between the expression intensities of specific antigens as well as between these expression intensities and distinct chromosome aberrations in B-LPD. However, the respective immunophenotype patterns were much more diverse and no strong correlations were found to most chromosome aberrations. Only in cases with t(11;14) or with t(8;14) strong correlations have been observed with highly significant differences in antigen expression as compared to cases with other cytogenetic aberrations. The data suggest that the biologic background in most B-LPD is heterogeneous from the diagnostic point of view which is in contrast to other and also genetically clearly defined hematologic malignancies such as CML or APL. To clarify the more diverse biology and its clinical significance also in conjunction with histologic findings further studies are warranted.