Prognostic Value of Fatty Acid Synthase and Spot14 in Diffuse Large B-Cell Lymphoma.
Olga V Danilova, Heather M Froehlich, Tarek Hammour, Nancy B Kuemmerle, Norman B Levy, William B Kinlaw, Prabhjot Kaur. Dartmouth-Hitchcock Medical Center, Lebanon, NH; Maine Medical Center, Portland; Dartmouth Medical School, Hanover, NH; Norris Cotton Cancer Center, Lebanon, NH
Background: Diffuse large B-cell lymphoma is the most common lymphoma in the western world. It has a heterogeneous clinical course with different treatment responses within the same diagnostic category, suggesting the need for reliable prognostic factors and novel therapeutic approaches. Recently metabolic pathways draw attention as the key players in carcinogenesis. Human fatty acid synthase (FASN), 270-kDa cytosolic dimeric enzyme is responsible for palmitate synthesis and energy supply. It has been shown to have prognostic significance in cancers of the prostate, breast, ovary. The prognostic value of FASN and “Spot 14” (THRSP, S14), nuclear activator of fatty acid synthesis has, to our knowledge, not been reported in DLBCL.
Design: A tissue microarray (TMA), containing 56 cases of DLBCL, diagnosed between 1999 and 2006, were analyzed by immunohistochemistry (IHC) for FASN and S14. Staining was graded as weak diffuse or strong diffuse and the results were correlated with stage, lactate dehydrogenase (LDH) level, IPI score, DLBCL subtype (germinal center vs non-germinal center) and overall survival. The DLBCL was subtyped by immunostaing with CD10, MUM1 and Bcl6 according to WHO 2008 criteria. Chi-square test (Χ2) was used to analyze the results.
Results: The patient population included 30 women and 26 men with mean age 62± 17.5yrs. Out of 56 patients, 24 died of disease, and 32 remained in complete remission after a median follow-up of 4.7 years (1.5-14.0 years). There was a statistically significant negative correlation between FASN expression pattern and overall survival (p=0.0003), IPI score (p=0.010) and LDH level (p=0.044). Interestingly, DLBCL subtype did not correlate with overall survival (p=0.375). There was no significant correlation between DLBCL subtype and disease stage with FASN staining (p>0.05). We did not observe any correlation between S14 staining and analyzed prognostic factors in DLBCL.
Conclusions: Overexpression of FASN emphasizes the role of fatty acid synthesis in the pathogenesis of DLBCL. Its differential overexpression defines a group of patients with a more aggressive course and has both prognostic and possible therapeutic implications. Further larger studies are however needed to validate these markers.
Monday, February 28, 2011 9:30 AM
Poster Session I Stowell-Orbison/Surgical Pathology/Autopsy Awards Poster Session # 180, Monday Morning