Prognostic relevance of apoptotic cell death in non-Hodgkin's lymphomas:
A multivariate survival analysis including Ki67 and p53 oncoprotein
expression
Aims: To evaluate the independent prognostic value of apoptotic versus
proliferative fractions in a series of 92 patients with non-Hodgkin’s
lymphomas (NHL).
Methods and results: Apoptotic fractions were quantified by use of the
TdT (terminal deoxynucleotidyl-transferase)mediated in-situ
end-labelling technique (TUNEL), the percentage of positive cells
constituting the apoptotic index (AI). Proliferative rate was expressed
as percentage of Ki67 positive cells (Ki67 LI), Tissues were also
stained for p53 protein with the DO-1 antibody. Patients were followed
up until death (n =33) or for an average of 63 months (n = 56). AI
increased with malignancy grade and proliferative activity but was not
related to location, cell of origin, clinical stage, bone marrow
involvement and p53 expression. In multivariate analysis, overall
survival was independently influenced by grade, stage, p53 LI and
chemotherapy. The independent predictors of disease-free survival were
Ki67 LI location and chemotherapy. AI turned out to be the only
independent (negative) predictor of post-relapse survival. On the other
hand, a low Ki67 LI increased the risk of relapse (logistic regression
analysis) whereas a low p53 LI increased the probability of complete
response,
Conclusions: Our results suggest that the combined assessment of
apoptotic fraction, proliferative rate and p53 expression may provide
important prognostic information independent of other
clinicopathological parameters in NHL
