CELLULAR DEATH IN NEUROBLASTOMA - IN-SITU CORRELATION OF APOPTOSIS AND BCL-2 EXPRESSION

Apoptosis is the selective physiologic: deletion of cells that are no longer required. Over-expression of the bcl-2 protooncogene extends su rvival of neurons otherwise destined for apoptosis. The unique capacit y of neuroblastoma (NB) to undergo spontaneous regression and the prog nostic dichotomy of children with this malignancy led us to evaluate b cl-2 expression and apoptosis in NE. An in situ DNA nick-labeling tech nique to detect apoptotic cells, as well as immunohistochemistry and m orphology, were utilized in a selection of NE tumor specimens and in t he human fetal sympathetic nervous system. bcl-2 expression was presen t in all 28 Mb tumors examined and in sympathetic ganglia of the human fetus. Measurement of overall bcl-2 expression and of extent of apopt osis correlated with favorable prognosis. In low-stage tumors, bcl-2 e xpression was most intense in poorly differentiated tumor cells adjace nt to fibrovascular stroma. Cells distant from the stroma exhibited in creasing degrees of chromaffin differentiation, with apoptosis most ev ident in bcl-2-negative neuroblasts adjacent to well-differentiated Mb cells. The spatial distribution of bcl-2 expression, apoptosis and ch romaffin differentiation in favorable-prognosis Mb may provide insight into mechanisms of persistent tumor existence or regression. (C) 1995 Wiley-Liss, inc.