Association of tumor-associated macrophages of M2 subtype with outcome in follicular lymphoma.

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8078 Background: Current methods used to prognosticate patients with follicular lymphoma (FL) include the Follicular Lymphoma International Prognostic Index (FLIPI) and tumor grade. However, they do not provide information on the biological and molecular features of FL. Recent data suggest that high tumor-associated macrophages (TAM) content may be an adverse prognostic factor in FL. However, TAM consists of two main subtypes, M1 and M2, with the former related to pro-inflammatory properties while the latter, anti-inflammatory functions. Currently, the prognostic impact of each individual subtype has not been elucidated and this may be more important than looking at TAM alone. Methods: Tumor specimens of 98 patients with FL diagnosed between 2005 and 2009 were investigated using immunohistochemistry and fluorescence in-situ hybridization (FISH) using break-apart FISH probes targeting BCL2, BCL6, MYC and IgH genes. Tumor specimens expressing a higher proportion of CD68+/CD163- in one high power field were defined as M1 subtype and those that expressed a greater proportion of CD68+/CD163+ were denoted as M2 subtype. Results: Amongst the 98 patients, 60 (61%) were of the M2 subtype, 59% presented with advanced disease, 47% were grade 3 and the median age was 59 years (21 – 88 years). Baseline characteristics including grade, stage and recurrent translocations did not significantly differ between the M1 and M2 groups. Similarly, there was also no difference in terms of treatment received (both Rituximab and chemotherapy) between the two groups. Despite these similarities, with a median follow-up of 3.2 years, the 3-year overall survival (OS) was significantly different (M1, 100% vs M2, 85%; p < 0.01). All 11 patients who died were of the M2 subtype (p=0.009). Conclusions: Our findings show that despite similar patient characteristics and treatment, there was, however, a statistically significant difference in OS, with the M2 subtype demonstrating an inferior outcome. The M2 TAM subtype rather than TAM alone may be a more important prognostic marker in FL, which could possibly be explained by its known biological anti-inflammatory function.