PROGNOSTIC RELEVANCE OF APOPTOTIC CELL-DEATH IN NON-HODGKINS-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 quanti fied by use of the TdT (terminal deoxynucleotidyl-transferase)mediated in-situ end-labelling technique (TUNEL), the percentage of positive c ells constituting the apoptotic index (AI). Proliferative rate was exp ressed as percentage of Ki67 positive cells (Ki67 LI), Tissues were al so stained for p53 protein with the DO-1 antibody. Patients were follo wed up until death (n =33) or for an average of 63 months (n = 56). AI increased with malignancy grade and proliferative activity but was no t related to location, cell of origin, clinical stage, bone marrow inv olvement and p53 expression. In multivariate analysis, overall surviva l was independently influenced by grade, stage, p53 LI and chemotherap y. The independent predictors of disease-free survival were Ki67 LI lo cation and chemotherapy. AI turned out to be the only independent (neg ative) predictor of post-relapse survival. On the other hand, a low Ki 67 LI increased the risk of relapse (logistic regression analysis) whe reas a low p53 LI increased the probability of complete response, Conc lusions: Our results suggest that the combined assessment of apoptotic fraction, proliferative rate and p53 expression may provide important prognostic information independent of other clinicopathological param eters in NHL.