Telomerase activity and proliferation index in aggressive mature B-cell lymphoma: comparison to germinal center phenotypic markers.
Cell proliferation may be evaluated by various methods, including Ki-67 immunohistochemistry and measures of telomerase activity. Both methods would theoretically show comparable increases in a given case. To evaluate the relationship between these 2 markers of proliferation in aggressive mature B-cell lymphomas, 48 cases were studied. The study group included 5 cases of mantle cell lymphoma (MCL); 6 cases of Burkitt's/Burkitt's-like lymphoma (BL); 9 cases of follicular lymphoma, grade 3 (FLC); and 28 cases of diffuse large B-cell lymphoma (DLC). Telomerase activity was measured as total product generated (TPG) units, and TPG results for the aforementioned cases were compared to the TPG results for 10 cases of reactive follicular hyperplasia. An overlap in TPG scores between reactive cases and lymphoma cases was found. Significant differences in both log TPG (P = 0.0443) and Ki-67 (P = 0.0006) were seen in the different lymphoma types. A positive correlation between Ki-67 percentage and TPG score was identified in FLC (r = 0.9281; P = 0.0003), but a poor correlation between these 2 indicators was seen in the other lymphoma types. Cluster analysis identified distinct patterns for MCL, FLC, and BL, but heterogeneous patterns for DLC. Because increases in both Ki-67 proliferation and telomerase activity are reported in normal germinal centers (GCs), these tests were also evaluated for usefulness as markers of a GC cell phenotype. Among the FLC and DLC cases, features of a GC phenotype significantly correlated with increased Ki-67 percentage (P = 0.0152), but not with increased log TPG. An elevated log TPG correlated with CD10 expression, and elevated Ki-67 percentage correlated with both CD10 and BCL-6 expression. TPG level and Ki-67 percentage did not correlate with the presence of t(14;18) or BCL-2 protein expression. Although the proliferation patterns were fairly distinctive for MCL, FLC, and BL, these studies show that markers of cell proliferation do not by themselves,identify distinct subtypes of large cell lymphomas. With the exception of FLC, the tumors exhibited poor correlation between telomerase activity and Ki-67 proliferation index. These tests did show some correlation with expression of GC cell phenotypic markers, however.
Chiu
Katharine C
KC
Division of Pathology, City of Hope National Medical Center, Duarte, CA, USA.
Fine
Miriam
M
Ikle
David
D
Slovak
Marilyn L
ML
Arber
Daniel A
DA
D014408:Biomarkers, Tumor / Q000378:metabolism*; D002455:Cell Division / Q000502:physiology; D004268:DNA-Binding Proteins / Q000378:metabolism; D018858:Germinal Center / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D017730:Ki-1 Antigen / Q000378:metabolism*; D016393:Lymphoma, B-Cell / Q000378:metabolism* / Q000473:pathology; D015260:Neprilysin / Q000378:metabolism; D010641:Phenotype; D016133:Polymerase Chain Reaction; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051560:Proto-Oncogene Proteins c-bcl-6; D019098:Telomerase / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D014408:Biomarkers, Tumor; D004268:DNA-Binding Proteins; D017730:Ki-1 Antigen; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D051560:Proto-Oncogene Proteins c-bcl-6; D014157:Transcription Factors; D019098:Telomerase; D015260:Neprilysin