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Measurement of growth fraction is an important way to provide an objective assessment of non-Hodgkin's lymphomas; however, many of the techniques used require fresh tissue and/or special instrumentation. Recently, antibodies to the proliferating cell nuclear antigen (PCNA)/cyclin reactive in paraffin-embedded sections have become available. To investigate the utility of one such antibody in the study of follicular center cell (FCC) lymphomas and cleaved cell lymphomas of centrocytic type (CC), paraffin sections from 40 cases that had been characterized in two previous morphometric studies were stained with a PCNA antibody. Strong correlations were found between PCNA staining in formalin- and B5-fixed tissues, between the overall proportion of PCNA-positive cells and the proportion in the area of greatest staining, and between strong and total staining. Proliferating cell nuclear antigen staining was significantly stronger in the noncleaved FCC lymphomas than in the cleaved cell lymphomas. The FCC lymphomas showed moderate to strong correlations between PCNA staining and morphometric features of transformation, but only nuclear area correlated with PCNA staining in the CC group. Proliferating cell nuclear antigen staining was not significantly different between CC lymphomas with and without the characteristic bcl-1/PRAD 1 gene rearrangement. In summary, PCNA staining of either B5- or formalin-fixed, paraffin-embedded tissue sections is a simple aid in the objective categorization of FCC lymphomas and may offer additional potentially prognostic information in some FCC subsets and in CC lymphomas. The findings further support the distinction between CC and true FCC lymphomas.

Centrocytic lymphomas are defined in the Kiel classification as B-cell lymphomas composed exclusively of cells resembling cleaved follicular center cells (FCC). These lymphomas have been shown to be histologically, immunophenotypically, and clinically distinct from other cleaved FCC lymphomas. DNA from 18 centrocytic lymphomas (14 patients) was analyzed using Southern blotting and probes for immunoglobulin heavy (JH) and kappa light chain (JK) joining gene, T-cell receptor beta chain constant gene (CB), bcl-1, bcl-2, and c-myc gene rearrangements. All of the lymphomas had JH and JK rearrangements, confirming their B-cell origin. None of the specimens had detectable CB, bcl-2, or c-myc rearrangements. However, 4 of 14 patients (28.6%) had rearrangement of the chromosome 11 bcl-1 locus. Therefore, centrocytic lymphomas are genotypically distinguishable from the majority of other small cleaved FCC lymphomas by their lack of demonstrable bcl-2 rearrangements. This supports the distinct nature of centrocytic lymphomas and suggests the lack of importance for the putative oncogene bcl-2 in these cases. Furthermore, the frequent rearrangement of bcl-1 suggests a possible role for this locus in the pathogenesis of at least some centrocytic lymphomas.