The Regulatory T-Lymphocyte Content of Post-Transplant Lymphoproliferative Disorders
J Vaughan, H Olteanu, B Wimpee, S Kroft, JA Jarzembowski. Medical College of Wisconsin, Milwaukee, WI
Background: Post-transplant lymphoproliferative disorders (PTLDs) occur in roughly 2% of solid organ or bone marrow (BM) transplant recipients, arising in patients of all ages and in a various anatomic sites. Regulatory T-lymphocytes (Tregs) are thought to play a role in developing self-tolerance and avoiding autoimmunity, and are distinguished by nuclear expression of Foxp3, a forkhead family transcription factor. Reports have demonstrated Tregs in solid tumors and aberrant Foxp3 expression by nonhematopoietic cells, suggesting possible mechanisms of immune evasion. Because PTLD arises in the setting of immune dysregulation, we wished to examine the content of Tregs within these lesions.
Design: Following institutional IRB approval, 43 adult and 10 pediatric PTLD cases with adequate formalin-fixed paraffin-embedded tissue were selected. Cases were reviewed for consensus diagnoses and included 18 polymorphic, 31 monomorphic, 3 Hodgkin lymphoma type, and 1 unclassifiable PTLDs. These were compared to 5 cases of diffuse large B-cell lymphoma (DLBCL), 5 hypertrophic tonsils, and 5 reactive lymph nodes. Immunostaining using antibodies against CD3, CD4, CD20, and TIA-1 was performed according to manufacturer's recommendations. Positive cells per high-power field (400x) were determined as an average of 10 fields, and compared between groups and to clinicopathologic data using Pearson correlation and Student's two-sided tests.
Results: There were 34 males and 19 females (1 to 69-years-old) including 12 BM and 40 solid organ transplants. Median follow-up was 5.5 years (range, 1-12). Overall, PTLDs had fewer Foxp3+ cells than benign lymphoid tissue (12.2 versus 57.4 / hpf; p = 0.007), but similar numbers to DLBCLs (6.0). The Treg content did not significantly differ between polymorphic and monomorphic PTLD (6.8 vs. 3.6, p = 0.54), nor between the Burkitt-, DLBCL-, and Hodgkin-like variants. Tregs did not vary with patient age, site of involvement, solid vs. BM transplant, or EBV positivity. Treg numbers trended with survival, but this did not reach statistical significance (p = 0.07). There was no co-expression of B-cell markers and Foxp3 on the neoplastic cells.
Conclusions: Tregs were markedly decreased in both PTLDs and DLBCLs compared to benign lymphoid tissue, and significant aberrant expression of Foxp3 on tumoral B-cells was not seen. The Treg content did not correlate with other clinicopathologic data. Further examination of the cellular composition of PTLDs might yet lead to improved diagnosis, classification, and treatment.
Monday, March 22, 2010 1:00 PM
Poster Session II # 134, Monday Afternoon