The clinical usefulness of histologic grading in follicular lymphoma (
FL) is controversial and is further compromised by the subjective natu
re and poor reproducibility of most systems in current use. Therefore,
we decided to objectively evaluate the importance of cellular prolife
ration in FL, along with the current grading systems. We studied 106 p
atients with FL who were uniformly staged and aggressively treated. A
proliferative index (PI) was determined quantitatively using an automa
ted image analyzer and a new Ki-67 antibody that stains archival paraf
fin tissues. The cases were also subclassified according to the Berard
, Rappaport, Luke-Collins, and Jaffe methods, and survival analysis wa
s performed. Patients with a low PI (<40%) had a significantly longer
overall survival (OS) than those with a high PI (greater than or equal
to 40%). but the PI did not predict failure-free survival (FFS). The
mean PI correlated well with the subgroups in each of the various clas
sifications. All four of the classification methods were predictive of
OS, but only the Berard method appeared to predict FFS and suggest th
at a proportion of patients with FL may be curable. In multivariate an
alysis. histologic classification was the only independent predictor o
f OS (Berard method: relative risk, 3.1) and the International Prognos
tic Index was the only independent predictor of FFS (relative risk, 2.
3). We conclude that the Berard method for grading of FL is clinically
useful and, along with the International Prognostic Index, should be
included in future clinical studies of FL. The measurement of cellular
proliferation does not appear to add additional useful information in
FL. (C) 1995 by The American Society of Hematology.