[1560] c-FLIP Correlates with Non-Germinal Center Subtype of Diffuse Large B-Cell Lymphoma

Swati Srivastava, Olga V Danilova, Alexey V Danilov, Norman B Levy, Prabhjot Kaur. Dartmouth Hitchcock Medical Center, Lebanon, NH

Background: Diffuse large B cell lymphoma (DLBCL) is a heterogeneous aggressive disease and 50% of the patients succumb to it despite anthracyclin based multi-agent treatment. c-FLIP is an antiapoptotic, NF-kB induced survival factor and regulates caspase 8-mediated pathway. Gene-expression profiling has shown c-FLIP to be expressed in ABC-like DLBCL, with prognostic implication. Studies using immunohistochemistry (IHC) have shown conflicting results on expression and prognostic significance (WHO-2008). mABs NF6 (1:10) and G11 (1:25) has been used before for specific detection of c-FLIP in paraffin- embedded tissue sections(see reference). Here, we assessed c-FLIP by IHC for prognostic significance in DLBCL.
Design: A tissue microarray, containing 87 cases of DLBCL, diagnosed between 1999 and 2008, were analyzed by IHC for c-FLIP (NF6; 1:15). Intensity of cytoplasmic staining was subjectively graded as negative, low and high. A cut-off value of >30% was called positive. Negative and low expression cases were combined; and results are reported as low vs. high expression. Results were correlated with survival, IPI score and subtype {germinal center-like (GCB) vs non-germinal center-like(non-GCB)}. DLBCL was subtyped by immunostaining according to WHO 2008 criteria. Chi-square test (χ2) was used for analysis.
Results: Male:Female ratio was 1:1, mean age 60.2± 19.3 yrs. Of 87 cases, 35 died of disease, 52 remained in complete remission after a median follow-up of 3.4 years. IPI score was a good predictor of survival in our cohort. c-FLIP expression studied on all cases did not correlate with survival or IPI (p>.05). However, of 62 cases that were classified as GCB and non-GCB type DLBCL, 48% non-GCB (15 out of 31) and 22% of GCB (7 out of 31) showed diffuse strong expression (p=.033).
Conclusions: We used mouse anti-human FLIP monoclonal antibody, unconjugated, clone NF6 at a dilution of 1:15 on DLBCL and obtained easily interpretable cytoplasmic staining. We have also shown a statistically significant histologic overexpression of c-FLIP in non-GCB versus GCB DLBCL. More studies on c-FLIP appear warranted to further elucidate its prognostic and therapeutic significance.
Category: Hematopathology

Tuesday, March 20, 2012 1:00 PM

Poster Session IV # 185, Tuesday Afternoon

 

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