Is the Sézary Cell Losing It? Cell Cycle Related Proteins in Lymph Nodes with Mycosis Fungoides.
Xingcao Nie, Rekha Bhat, Essel Dulaimi Al-Saleem, Eric Vonderheid, J Steve Hou. Drexel University College of Medicine, Philadelphia, PA; Johns Hopkins Medical Institutes, Baltimore, MD
Background: Abnormalities of cell cycle and apoptosis related proteins have been examined in Mycosis Fungoides (MF), but their roles in lymph node involvement and disease progression have not been reported. We investigated the expression of cell cycle and apoptosis related proteins (Rb, p53, Bcl-2, p27) in lymph nodes involved with MF.
Design: Paraffin blocks of lymph nodes from 51 patients with MF (1991-2010) were used to construct a tissue microarray. 51 MF patients had either a diagnosis of dermatopathic lymphadenopathy (DL: 34/51) or lymph nodes involved with MF (MF-LN: 17/51). Clinical data was available on 27 patients, of which a majority were non-skin confined MF [MF with erythroderma (MFE)=7; Sézary Syndrome (SS)=11]. Benign lymph nodes (N=15) were used as control. Immunohistochemical (IHC) staining using antibodies to Rb, p53, Bcl-2, p27, CD3, CD4 and semi-quantitation of the staining in the interfollicular zone were performed. Rb and p53 were graded as <5%, 5-20% and >20%; Bcl-2 and p27 were graded as <30%, 30-60% and >60%. SPSS software was used for analysis (p<0.05).
Results: A significant number of lymph nodes from patients with MF had less than 20% expression of Rb as compared to benign lymph nodes (39/51 vs. 10/17, p<0.05). Similarly, a decrease in Bcl-2 expression in the interfollicular T cells was noted in MF as compared to B-LN (43/51 vs. 14/15, p<0.05). No difference was observed in Rb and Bcl-2 expression between MF-LN and DL. Decreased p27 and increased p53 expression were demonstrated in MF-LN, compared to DL or benign lymph nodes. Additionally, p53 positivity was noted mainly in large cells in MF-LN. Loss of Rb and Bcl-2 was noted in a majority of lymph nodes with clinical diagnoses of SS or MFE (76% and 71%, respectively). Decreased expression of p27 (7/17, 41%) and increased p53 expression (3/17, 18%) was observed in the same population.
Conclusions: 1. The neoplastic lymphocytes in MF-LN were more likely to lose expression of Rb, Bcl-2, p27 and to have increased p53 expression. The loss of cell cycle regulatory proteins (Rb and Bcl-2) correlates with higher clinical stage, which may play a role in disease progression. 2. Loss of p27 and increased p53 may also participate in disease progression. The increased p53 expression might represent mutated/inactivated p53. Hypermethylation studies are underway to further address this question.
Tuesday, March 1, 2011 9:30 AM
Poster Session III # 230, Tuesday Morning