N-MYC AMPLIFICATION AND CELL-PROLIFERATION RATE IN HUMAN NEUROBLASTOMA

In neuroblastoma, N-myc amplification has been found to be strikingly associated with rapid tumour progression and poor prognosis, Recent st udies have demonstrated that cell proliferative activity also signific antly predicts the clinical outcome in patients with neuroblastoma, In order to define the correlation between N-myc amplification and cell proliferation rate, in the present investigation the two parameters me re first assessed in 48 neuroblastoma tumours. N-myc amplification was evaluated in frozen specimens by Southern-blot analysis using the NB 19-21 probe and it was detected in nine patients, Cell proliferative a ctivity was determined by measuring the AgNOR protein area in histolog ical sections selectively stained bq silver, The mean AgNOR protein ar ea value of neuroblastomas with N-myc amplification (3.63 +/- 1.62 mu m(2)) was not significantly different from that of neuroblastomas with out N-myc amplification (2.46 +/- 1.57 mu m(2); P=0.30). On the other hand, both N-myc amplification and AgNOR protein expression were found to be significantly related to the clinical outcome of the disease (P <0.001 and P=0.0143, respectively; median follow-up time=47 months; ra nge 18-106 months), in a second set of experiments, the relationship b etween N-myc amplification and cell proliferation rate was assessed in seven established human neuroblastoma cell lines. N-myc amplification was found to be completely independent of the population doubling tim e (DT), which, on the contrary, was strictly related to the quantitati ve expression of AgNOR protein (r=-0.947; P<0.001). Altogether, the pr esent results indicate that N-myc amplification and cell proliferation rate are not interrelated in neuroblastoma, each representing an inde pendent biological parameter of cancer cells associated with the clini cal behaviour of the disease. (C) 1997 John Wiley & Sons, Ltd.