Tumor sclerosis but not cell proliferation or malignancy grade is a prognostic marker in advanced-stage follicular lymphoma: the German Low Grade Lymphoma Study Group.
OBJECTIVE
Follicular lymphoma is an indolent lymphoma with a long median overall survival. However, a considerable number of patients die within the first 2 years after the onset of the disease. Because the treatment options vary with respect to antitumor effect and potential toxic adverse effects, the identification of high-risk patients would be helpful in directing therapeutic decisions in individual patients. Several histopathologic biomarkers for risk stratification have been suggested, but most markers have not been validated in patients treated in prospective trials.


METHODS
We report a comprehensive approach to evaluate histopathologic biomarkers, including WHO grade, histology, and proliferation and quantitation of immune bystander cells, in 158 patients with nodal advanced-stage follicular lymphoma treated first line within a randomized trial.


RESULTS
Tumor sclerosis was a significant prognostic marker of poor overall survival that was independent of the Follicular Lymphoma International Prognostic Index (FLIPI). WHO grade, proliferation, and total T-cell or macrophage content were not associated with overall survival.


CONCLUSIONS
The presence of sclerosis within the lymphoma is a marker of poor overall survival that is independent of the FLIPI. The quantification of macrophage or absolute T-cell content, grading, and proliferation are of no help in predicting the outcome of FL. Future studies need to identify surrogate markers for the prognostic immune signatures identified by gene expression profiling. Most importantly, new prognostic markers need to be confirmed in patients treated within prospective trials.
Klapper
Wolfram
W
Department of Pathology, Hematopathology Section and Lymph Node Registry, Kiel, Germany. wklapper@path.uni-kiel.de
Hoster
Eva
E
Rölver
Lars
L
Schrader
Carsten
C
Janssen
Dirk
D
Tiemann
Markus
M
Bernd
Heinz-Wolfram
HW
Determann
Olaf
O
Hansmann
Martin-Leo
ML
Möller
Peter
P
Feller
Alfred
A
Stein
Harald
H
Wacker
Hans-Heinrich
HH
Dreyling
Martin
M
Unterhalt
Michael
M
Hiddemann
Wolfgang
W
Ott
German
G
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis*; D003131:Combined Modality Therapy; D005260:Female; D005858:Germany / Q000453:epidemiology; D006801:Humans; D007150:Immunohistochemistry; D016898:Interferon-alpha / Q000008:administration & dosage; D008224:Lymphoma, Follicular / Q000401:mortality / Q000473:pathology* / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009367:Neoplasm Staging; D011379:Prognosis; D016016:Proportional Hazards Models; D016032:Randomized Controlled Trials as Topic; D018570:Risk Assessment; D012598:Sclerosis; D018709:Statistics, Nonparametric; D033581:Stem Cell Transplantation; D016019:Survival Analysis
D014408:Biomarkers, Tumor; D016898:Interferon-alpha