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Published on: July 20, 2016
Cell kinetic analysis of interleukin-2 receptor-tested chronic lymphocytic leukemia using the AgNOR silver stain
W A Mourad1, W C Pugh, Y O Huh
1Department of Pathology, University of Texas M.D. Anderson Cancer Center, Houston.
Insights
Interleukin-2 receptor (IL-2R/CD25) positive B-cell chronic lymphocytic leukemia (B-CLL) cases show significantly higher proliferative activity. This suggests IL-2R positivity may identify a distinct B-CLL subgroup with increased cell turnover.
Area of Science:
- Hematology
- Oncology
- Cell Biology
Background:
- B-cell chronic lymphocytic leukemia (B-CLL) is typically a low-grade malignancy.
- Interleukin-2 receptor (IL-2R/CD25) expression on lymphocytes correlates with increased proliferative activity.
- Argyrophilic nucleolar organizer regions (AgNORs) are markers of cellular proliferation and ploidy.
Purpose of the Study:
- To investigate the correlation between IL-2R/CD25 expression and proliferative activity in B-CLL.
- To differentiate B-CLL subgroups based on IL-2R expression using AgNOR counting methods.
Main Methods:
- Bone marrow specimens from 32 B-CLL patients were analyzed.
- Immunohistochemistry for IL-2R/CD25 and silver staining for AgNORs were performed.
- Two AgNOR counting methods, mean AgNOR (mAgNOR) for ploidy and percentage of nuclei with >= 5 AgNORs (pAgNOR) for proliferation, were applied.
Main Results:
- No significant difference in bone marrow morphology between IL-2R-negative and IL-2R-positive groups.
- IL-2R-positive B-CLL cases showed a male predominance and a preponderance of lambda light chain expression.
- All cases had mAgNOR counts within the diploid range.
- IL-2R-positive B-CLL exhibited significantly higher pAgNOR values (mean 10.20%) compared to IL-2R-negative cases (mean 2.31%; P < .0001).
Conclusions:
- IL-2R/CD25 positivity in B-CLL is associated with significantly higher proliferative activity, as indicated by pAgNOR counts.
- IL-2R-positive B-CLL may represent a distinct subgroup with increased cellular proliferation.
- These findings highlight the potential clinical significance of IL-2R expression in B-CLL prognostication.
Abstract:
B-cell chronic lymphocytic leukemia (B-CLL) is typically a low-grade neoplasm with a diploid DNA index and low proliferative activity. Interleukin-2 receptor (IL-2R/CD25) positivity often indicates increased proliferative activity and activation in both T and B lymphocytes. The argyrophilic nucleolar organizer regions (AgNORs) are loops of DNA identified by a silver staining technique and have been correlated with ploidy and proliferative activity. Two distinct AgNOR counting methods have been previously shown to correlate with DNA ploidy and proliferative activity, respectively: the mean AgNOR count (mAgNOR) correlates more with ploidy, and the percentage of nuclei with > or = 5 AgNORs/nucleus (pAgNOR) reflects proliferative activity. We studied bone marrow specimens from 32 patients with B-CLL using both anti-IL-2R on the marrow aspirates and the AgNOR silver stain on marrow biopsy specimens, applying both AgNOR counts. All tumors were CD5+, CD19+, and CD19/CD20+. Sixteen tumors were IL-2R- (< 20% IL-2+ B cells), and 16 were IL-2R+ (> or = 20% IL-2R+ B-cells). No significant difference in morphology of bone marrow involvement was noted in the two groups. A male predominance was noted in the IL-2R+ group of patients (3:1). There was also a preponderance of lambda light chain expression in the IL-2R+ tumors (11/16) compared with the IL-2R- cases (5/16). Except for two cases, all tumors had mAgNOR counts within the diploid range (< 2.4). The 16 IL-2R- tumors had pAgNOR in the range of 0% to 7% (mean, 2.31 +/- 2.18 standard deviation), whereas the IL-2R+ tumors had pAgNOR ranging from 6% to 15% (mean, 10.20 +/- 2.70 standard deviation; P < .0001). This finding suggests that IL-2R+ B-CLL might represent a subgroup of tumors with higher proliferative activity.
