Prognostic significance of the proliferative activity in neuroblastoma

The prognostic significance of the immunohistochemically assessed growth fraction in neuroblastomas was determined in relation to tumor grade and tumor stage. A total of 101 cases of neuroblastoma were examined with the monoclonal antibodies PC10 against proliferating cell nuclear antigen (PCNA) and Ki-S5 against the Ki-67 protein. Patients were followed for a mean time of 4.8 years. Expression of both PC10 and Ki-S5 was found to be significantly linked to tumor grade and tumor stage. Prognostically favorable stage IVs was associated with low PCNA and Ki-S5 levels. For ganglioneuroblastoma, significant differences were found between the diffuse and the composite type. In univariate analysis of stage III and IV tumors, Ki-S5 and PCNA scores were significantly correlated with disease-free survival (P < 0.0015), allowing definition of a subset of cases with favorable outcome. As to Shimada's group with poor prognosis, significant differences in the clinical course were found for low and high Ki-S5 scores (P = 0.036) but not for PCNA. In multivariate analysis, only patient age, Shimada's grade, and Ki-S5 scores achieved prognostic significance. We conclude that proliferation marker Ki-S5 may provide substantial prognostic information and might become a useful adjunct for predicting the clinical courses of neuroblastoma.