Role of Foxp3+ T Lymphocytes in Lymph Nodes with Mycosis Fungoides Involvement
R Bhat, B Khandpur, JS Hou, E Vonderheid. Drexel University College of Medicine, Philadelphia, PA
Background: The objective of our study was to elucidate the role of DNA mismatch repair defects and microsatellite instability markers and Foxp3+ CD4+ CD25+ regulatory T cells (Tregs) in lymph node involvement with mycosis fungoides and correlate them with clinical data and flow analysis.
Design: Archived paraffin blocks with lymph nodes from 30 patients with Mycosis Fungoides (1991-2001) were used to construct a tissue microarray (2 cores/case) using an adhesive tape embedding system. Nine benign lymph nodes were used as control. Immunohistochemical (IHC) staining using antibodies to FOXP3, MLH1, MSH2, MSH6, CD3 and CD4 was performed. Foxp3+ CD4+ cells in the interfollicular zone were semi-quantitatively estimated as <10%, 10-50% and >50%. Microsatellite instability (MSI) markers were graded as absent/reduced or present with absence of any single marker classified as MSI present. Scanscope XT (Aperio, Vista, CA) was used to evaluate the microarray slides. SPSS software was used for analysis.
Results: 25/30 patients had skin involvement data available (Patch – 4/25; Plaque - 2/25; Tumor - 4/25 tumor; Erythroderma - 8/25; Sezary Syndrome - 7/25). 30 MF patients had either a diagnosis of dermatopathic lymphadenitis (DL ; 17/30) or cutaneous T cell lymphoma (CTCL; 13/30). Patients with CTCL in lymph nodes were more likely to have Sezary Syndrome (6/13), when compared to patients with DL (p<.05). National Cancer Institute-Veterans Administration (NCI-VA) staging on 29/30 cases showed 13 CTCL cases graded as either LN3or LN4; while DL cases graded LN1or LN2. Flow data was available in 31 cases (22 MF and 9 benign). 3/17 patients with DL and 8/13 with CTCL had abnormal flow cytometry results. A significant number of cases with CTCL had Foxp3 levels of less than 10%, when compared to DL (p<0.05). There was significant correlation with Foxp3+ levels on immunohistochemistry and CD25 percentage by flow analysis (21/30). All cases with FOX P3 results of <10% by IHC (3/19) had <2.0% CD25 positive cells. No difference was seen between benign controls and lymph nodes involved by MF in MSI markers.
Conclusions: Decrease in Foxp3+ Tregs correlates with lymph node involvement in patients with Mycosis Fungoides and possibly plays a role in disease progression. Larger studies with additional T cell lymphomas are underway to further elucidate the role of Foxp3+ Tregs and their contribution in disease progression.
Monday, March 22, 2010 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 60, Monday Morning