| dc.description.abstract | The natural history of follicular lymphoma is heterogeneous with numerous relapses
and remissions over many years. A substantial number of patients suffer an
aggressive disease course with death due to disease within 5 years of diagnosis. The
prognosis is significantly worse in patients (10-68%) who transform to an aggressive
histology. The clinical parameters used to stratify patients with this disease have
limited discriminative power and new prognostic biomarkers are required. Insights
into the biology of the disease, with identification of potential therapeutic targets are
also required. Analysis of paraffin embedded diagnostic FL biopsies from
populations of patients at the extremes of overall survival (<5 years and >15 years)
demonstrated that expression of CD4 T lymphocytes and a perifollicular location of
forkhead box protein P3 were significantly more common in diagnostic biopsies
from patients who lived >15 years. Patients with high numbers of intrafollicular CD4
T lymphocytes and higher numbers of CD68 positive macrophages were more likely
to undergo rapid transformation to diffuse large B cell lymphoma (DLBCL).
Analysis of sequential biopsies pre-and post-transformation from patients with FL
who subsequently transformed to DLBCL demonstrated high numbers of CD68
positive macrophages in the majority of cases. The overall survival from
transformation was reduced in patients in whom the number of FOXP3 positive T
cells decreased/remained low compared to patients in whom the number of FOXP3
positive T cells increased/remained high.
Analysis of biopsies pre-and post-transformation from patients with FL who
subsequently transformed, identified mutation of TP53 in 28% of cases suggesting a
limited role in the process of transformation. The immunocytochemical expression of
MDM2, the TP53 regulator, was significantly higher on transformation. The
phenotype of transformed FL was confirmed immunocytochemically as Germinal
Centre type and two potential drug targets, Aurora Kinase B and nm23, were
confirmed as being up-regulated on transformation. | en_US |
