Gene-expression and immunohistochemical study of specific T-cell subsets and accessory cell types in the transformation and prognosis of follicular lymphoma.
OBJECTIVE
Despite the generally favorable clinical course in follicular lymphoma (FL), a minority of patients have a poor prognosis-with death within 3 years of diagnosis-most often due to transformation to aggressive disease.


METHODS
In this study, we analyzed the potential of predicting early transformation on the basis of gene expression and immunologic parameters in FL biopsy samples taken at diagnosis.


RESULTS
At the gene-expression level, FL is a highly uniform disease at the time of diagnosis, precluding the detection of sufficiently validated prognostic gene-expression profiles suitable for a clinical setting. Combinations of differentially expressed genes indicate that immunologic mechanisms play a differential role in the risk of early transformation. Using immunohistochemistry for specific cell populations, the spatial distribution to neoplastic follicles and the activation of CD4-positive T-helper cells (P = .002) and specifically T-helper 1 (P = .004) were shown to be highly discriminatory to predict early transformation. A role for functional modulation of follicular dendritic cells could also be supported (P = .04). Other cell populations, including CD68-positive macrophages and regulatory T cells, were not differentially present.


CONCLUSIONS
These results support the identification of FL as an immunologically functional disease in which an interaction of the tumor cells and the functional composition of the microenvironment determines the clinical behavior.
Glas
Annuska M
AM
Department of Pathology, The Netherlands Cancer Institute, Amsterdam, The Netherlands.
Knoops
Laurent
L
Delahaye
Leonie
L
Kersten
Marie José
MJ
Kibbelaar
Robby E
RE
Wessels
Lodewyk A
LA
van Laar
Ryan
R
van Krieken
J Han J M
JH
Baars
Joke W
JW
Raemaekers
John
J
Kluin
Philip M
PM
van't Veer
Laura J
LJ
de Jong
Daphne
D
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015496:CD4-Positive T-Lymphocytes; D002471:Cell Transformation, Neoplastic; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007150:Immunohistochemistry; D008224:Lymphoma, Follicular / Q000235:genetics* / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011237:Predictive Value of Tests; D011379:Prognosis; D012189:Retrospective Studies; D016176:T-Lymphocyte Subsets; D006377:T-Lymphocytes, Helper-Inducer